The landscape of tumor microenvironment(TME)research has un-dergone rapid transformation over the past decade.1,2 As we deepen our understanding of the TME’s role in cancer progression,immune response modulation,and ...The landscape of tumor microenvironment(TME)research has un-dergone rapid transformation over the past decade.1,2 As we deepen our understanding of the TME’s role in cancer progression,immune response modulation,and therapeutic efficacy,this special issue,“Tumor Microen-vironment and Immunotherapy:From Bench to Bedside,”brings forth the latest breakthroughs in these domains.It highlights the interplay be-tween the TME,immune system dynamics,and cancer therapies,with a particular emphasis on precision medicine and the development of targeted treatments.展开更多
Approximately half of all cancers have p53 inactivating mutations,in addition to which most malignancies inactivate the p53 pathway by increasing p53 inhibitors,decreasing p53 activators,or inactivating p53 downstream...Approximately half of all cancers have p53 inactivating mutations,in addition to which most malignancies inactivate the p53 pathway by increasing p53 inhibitors,decreasing p53 activators,or inactivating p53 downstream targets.A growing number of researches have demonstrated that p53 can influence tumor progression through the tumor microenvironment(TME).TME is involved in the process of tumor development and metastasis and affects the clinical prognosis of patients.p53 participates in host immunity and engages in the immune landscape of the TME,but the specific mechanisms remain to be investigated.This review briefly explores the interactions between different states of p53 and TME components and their mechanisms,as well as their effects on tumor progression.To understand the progress of drug development and clinical studies related to p53 and tumor microenvironment.展开更多
BACKGROUND In recent years,numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment(TIME).However,to date,no systematic study has been conducted ...BACKGROUND In recent years,numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment(TIME).However,to date,no systematic study has been conducted on the relationship between gut microbiota and the TIME using bibliometric methods.AIM To describe the current global research status on the correlation between gut microbiota and the TIME,and to identify the most influential countries,research institutions,researchers,and research hotspots related to this topic.METHODS We searched for all literature related to gut microbiota and TIME published from January 1,2014,to May 28,2024,in the Web of Science Core Collection database.We then conducted a bibliometric analysis and created visual maps of the published literature on countries,institutions,authors,keywords,references,etc.,using CiteSpace(6.2R6),VOSviewer(1.6.20),and bibliometrics(based on R 4.3.2).RESULTS In total,491 documents were included,with a rapid increase in the number of publications starting in 2019.The country with the highest number of publications was China,followed by the United States.Germany has the highest number of citations in literature.From a centrality perspective,the United States has the highest influence in this field.The institutions with the highest number of publications were Shanghai Jiao Tong University and Zhejiang University.However,the institution with the most citations was the United States National Cancer Institute.Among authors,Professor Giorgio Trinchieri from the National Institutes of Health has the most local impact in this field.The most cited author was Fan XZ.The results of journal publications showed that the top three journals with the highest number of published papers were Frontiers in Immunology,Cancers,and Frontiers in Oncology.The three most frequently used keywords were gut microbiota,tumor microenvironment,and immunotherapy.CONCLUSION This study systematically elaborates on the research progress related to gut microbiota and TIME over the past decade.Research results indicate that the number of publications has rapidly increased since 2019,with research hotspots including“gut microbiota”,“tumor microenvironment”and“immunotherapy”.Exploring the effects of specific gut microbiota or derived metabolites on the behavior of immune cells in the TIME,regulating the secretion of immune molecules,and influencing immunotherapy are research hotspots and future research directions.展开更多
Severe tissue defects present formidable challenges to human health,persisting as major contributors to mortality rates.The complex pathological microenvironment,particularly the disrupted immune landscape within thes...Severe tissue defects present formidable challenges to human health,persisting as major contributors to mortality rates.The complex pathological microenvironment,particularly the disrupted immune landscape within these defects,poses substantial hurdles to existing tissue regeneration strategies.However,the emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine,providing encouraging prospects for tissue regeneration and restoration.This review aims to gather recent advances in immunomodulatory nanomedicine to foster tissue regeneration.We begin by elucidating the distinctive features of the local immune microenvironment within defective tissues and its crucial role in tissue regeneration.Subsequently,we explore the design and functional properties of immunomodulatory nanosystems.Finally,we address the challenges and prospects of clinical translation in nanomedicine development,aiming to propose a potent approach to enhance tissue regeneration through synergistic immune modulation and nanomedicine integration.展开更多
The presence of impurities in phosphogypsum has long impeded its effective utilization,highlighting the need for energy-efficient and sustainable purification methods.This study proposes a novel purification strategy ...The presence of impurities in phosphogypsum has long impeded its effective utilization,highlighting the need for energy-efficient and sustainable purification methods.This study proposes a novel purification strategy that synergistically combines pH regulation and micelle-assisted treatment to create an optimized microenvironment for impurity removal.Under mechanical grinding conditions,this approach enhances the rheological properties of the phosphogypsumslurries and facilitates the dissolution and removal of impurity ions.Experimental results demonstrate that the synergistic method achieves a remarkable 64.01%increase in whiteness while significantly reducing soluble phosphorus and fluoride content in a single-step process.This technique not only achieves high purification efficiency but also offers a practical pathway for the high-value utilization of phosphogypsum.These findings suggest that this method has substantial potential for enhancing sustainable resource management and enabling broader industrial applications of purified phosphogypsum.展开更多
Therapy-induced modulation of the tumor microenvironment(TME)to overcome the immunosuppressive TME is considered to be a chance for cancer treatment.Herein,we prepared near-infrared absorbing aza-BODIPY PhEt-azaBDP wi...Therapy-induced modulation of the tumor microenvironment(TME)to overcome the immunosuppressive TME is considered to be a chance for cancer treatment.Herein,we prepared near-infrared absorbing aza-BODIPY PhEt-azaBDP with 1-phenylethyl group at 1,7-sites,a type I photodynamic-photothermal therapy(PDT-PTT)agent.Self-assembly PhEt-azaBDP nanoparticles(NPs)can provide combined phototherapeutic effects under light irradiation and simultaneously induce inflammatory TME,by monitoring tumorassociated macrophages(TAMs)repolarization.Utilizing cluster of differentiation 86(CD86)and CD163 as the M1-type marker and M2-type marker respectively,PhEt-azaBDP NPs resulted in the increasement of the expression of CD86 and the decreasement of the expression of CD163 in TAMs under near-infrared(NIR)light irradiation,promoting TAMs to switch from M2-phenotype to M1-phenotype.Inflammatory cytokines,interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α),could be the key cytokine involved in the phototherapy-induced TME reprogramming.PhEt-azaBDP NPs could be a potential theranostic scaffold for the simultaneous induction and detection of TME reprogramming triggered by phototherapy.展开更多
Breast cancer is one of the most common malignancies worldwide and is a major cause of cancer-related mortality among women.Beyond tumor cells,the tumor microenvironment(TME)also plays an important role in cancer prog...Breast cancer is one of the most common malignancies worldwide and is a major cause of cancer-related mortality among women.Beyond tumor cells,the tumor microenvironment(TME)also plays an important role in cancer progression,therapy resistance,and metastasis.The TME is a complex ecosystem consisting of stromal and immune cells,extracellular matrix(ECM),and various signaling molecules that dynamically interact with tumor cells.Cancer-associated fibro-blasts remodel the ECM and secrete growth factors that promote tumor growth and invasion.Immune cells,such as tumor-associated macrophages,regulatory T cells,and myeloid-derived suppressor cells,often contribute to an immunosup-pressive environment that hinders anti-tumor immune responses.The ECM pro-vides structural support and acts as a reservoir for signaling molecules that in-fluence cancer cell behavior.These components evolve together with tumor cells,facilitating immune evasion,therapy resistance,and epithelial-to-mesenchymal transition,which promotes metastasis.Understanding these interactions is nece-ssary to develop novel therapeutic strategies that target both tumor and micro-environmental components.This minireview highlights the key stromal and immune elements within the breast cancer microenvironment,discussing their individual and collective roles in tumor progression and clinical outcomes,while emphasizing emerging therapeutic approaches aiming to reprogram the TME to improve treatment efficacy.展开更多
Sorafenib(Sora)not only has an inhibitory effect on angiogenesis via indirectly inhibiting tumor growth through antiangiogenesis,but also can inactivate the glutathione peroxidase 4(GPX4)to induce ferroptosis.Nonethel...Sorafenib(Sora)not only has an inhibitory effect on angiogenesis via indirectly inhibiting tumor growth through antiangiogenesis,but also can inactivate the glutathione peroxidase 4(GPX4)to induce ferroptosis.Nonetheless,the therapeutic efficacy is hampered by a plethora of factors,including low bioavailability and tumor microenvironment(TME).Of particular note is the hypoxic and reductive TME,which acts as a significant impediment and poses formidable challenges to attain the most optimal treatment outcomes.Herein,we developed a novel therapeutic platform based on Sora-loaded mesoporous ferromanganese nanoparticles(PMFNs@Sora).PMFNs mimics both catalase and GPX activities.The self-sustained catalase activity enables continuous decomposition of hydrogen peroxide to generate oxygen,which alleviates hypoxia microenvironment.The GPX activity simultaneously amplifies the therapeutic efficacy of Sora.The as-synthesized PMFNs@Sora demonstrates significantly enhanced antitumor effect in vitro through apoptosis-ferroptosis,revealed by Western blot.Furthermore,PMFNs@Sora also showed effective tumor growth inhibition in vivo.This multifunctional nanoplatform offers a promising strategy for modulating the TME and enhancing cancer treatment in clinical application.展开更多
The development of solid frustrated Lewis pairs(FLPs)catalysts with porous structures is a promising strategy for advancing green hydrogenation technologies and has garnered significant attention.Leveraging the divers...The development of solid frustrated Lewis pairs(FLPs)catalysts with porous structures is a promising strategy for advancing green hydrogenation technologies and has garnered significant attention.Leveraging the diverse oxidation states and structural tunability of cerium-based metal-organic frameworks(Ce-MOFs),this study employed a competitive coordination strategy utilizing a single carboxylate functional group ligand to construct a series of MOF-808-X(X=-NH_(2),-OH,-Br,and-NO_(2))featuring rich solid-state FLPs for hydrogenation of unsaturated olefins.The-X functional group serves as a microenvironment,enhancing hydrogenation activity by modulating the electronic properties and acid-base characteristics of the FLP sites.The unique redox properties of elemental cerium facilitate the exposure of unsaturated Ce sites(Ce-CUS,Lewis acid(LA))and adjacent Ce-OH(Lewis base(LB))sites within the MOFs,generating abundant solid-state FLP(Ce-CUS/Ce-OH)sites.Experimental results demonstrate that Ce-CUS and Ce-OH interact with theσandσ^(*)orbitals of H-H,and this"push-pull"synergy promotes heterolytic cleavage of the H-H bond.The lone pair electrons of the electron-donating functional group are transmitted through the molecular backbone to the LB site,thereby increasing its strength and reducing the activation energy required for H_(2)heterolytic cleavage.Notably,at 100℃and 2 MPa H_(2),MOF-808-NH_(2)achieves complete conversion of styrene and dicyclopentadiene,significantly outperforming MOF-808.Based on in-situ analysis and density functional theory calculations,a plausible reaction mechanism is proposed.This research enriches the theoretical framework for unsaturated olefin hydrogenation catalysts and contributes to the development of efficient catalytic systems.展开更多
Background:Previous researches mainly focused on whether cancer stem cells exist in diffuse large B-cell lym-phoma(DLBCL).However,subgroups with dismal prognosis and stem cell-like characteristics have been over-looke...Background:Previous researches mainly focused on whether cancer stem cells exist in diffuse large B-cell lym-phoma(DLBCL).However,subgroups with dismal prognosis and stem cell-like characteristics have been over-looked.Methods:Using large scale data(n=2133),we conducted machine learning algorithms to identify a high risk DLBCL subgroup with stem cell-like features,and then investigated the potential mechanisms in shaping this subgroup using transcriptome,genome and single-cell RNA-seq data,and in vitro experiments.Results:We identified a high-risk subgroup(25.6%of DLBCL)with stem cell-like characteristics and dismal prog-nosis.This high-risk group(HRG)was featured by upregulation of key enzyme(ODC1)in polyamine metabolism and cold tumor microenvironment(TME),and had a poor prognosis with lower 3-year overall survival(OS)(54.3%vs.83.6%,P<0.0001)and progression-free survival(PFS)(42.8%vs.74.7%,P<0.0001)rates com-pared to the low-risk group.HRG also exhibited malignant proliferative phenotypes similar to Burkitt lymphoma.Patients with MYC rearrangement,double-hit,double-expressors,or complete remission might have either favor-able or poor prognosis,which could be further distinguished by our risk stratification model.Genomic analysis revealed widespread copy number losses in the chemokine and interferon coding regions 8p23.1 and 9p21.3 in HRG.We identified ODC1 as a therapeutic vulnerability for HRG-DLBCL.Single-cell analysis and in vitro ex-periments demonstrated that ODC1 overexpression enhanced DLBCL cell proliferation and drove macrophage polarization towards the M2 phenotype.Conversely,ODC1 inhibition reduced DLBCL cell proliferation,induced cell cycle arrest and apoptosis,and promoted macrophage polarization towards the M1 phenotype.Finally,we developed a comprehensive database of DLBCL for clinical application.Conclusions:Our study effectively advances the precise risk stratification of DLBCL and reveals that ODC1 and immune-deserted microenvironment jointly shape a group of DLBCL patients with stem cell-like features.Target-ing ODC1 regulates immunotherapies in DLBCL,offering new insights for DLBCL treatment.展开更多
Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due...Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.展开更多
Computed tomography-based deep learning radiomics provides a novel,noninvasive approach to predicting the tumor immune microenvironment in colorectal cancer,revolutionizing precision oncology.The retrospective study b...Computed tomography-based deep learning radiomics provides a novel,noninvasive approach to predicting the tumor immune microenvironment in colorectal cancer,revolutionizing precision oncology.The retrospective study by Zhou et al analyzed preoperative computed tomography scans from 315 patients using convolutional neural networks,achieving robust predictive performance(area under the curve:0.851-0.892)for critical tumor immune microenvironment features,such as tumor-stroma ratio and lymphocyte infiltration,without requiring invasive biopsies.This editorial explores how this technique advances personalized immunotherapy,chemotherapy,and targeted therapies;challenges conventional oncology practices;and paves the way for a future of precision medicine.By integrating advanced imaging with immune profiling,deep learning radiomics redefines colorectal cancer management,highlighting the need to reevaluate the interplay of technology,biology,and ethics in gastrointestinal oncology.展开更多
The oviduct epithelium is the initial maternal contact site for embryos after fertilization,offering the microenviron-ment before implantation.This early gestation period is particularly sensitive to stress,which can ...The oviduct epithelium is the initial maternal contact site for embryos after fertilization,offering the microenviron-ment before implantation.This early gestation period is particularly sensitive to stress,which can cause reduced fertil-ity and reproductive disorders in mammals.Nevertheless,the local impact of elevated stress hormones on the ovi-duct epithelium has received limited attention to date,except for a few reports on polyovulatory species like mice and pigs.In this study,we focused on the effects of chronic maternal stress on cattle,given its association with infertil-ity issues in this monoovulatory species.Bovine oviduct epithelial cells(BOEC)differentiated at the air–liquid interface(ALI)were stimulated with 250 nmol/L cortisol for 1 or 3 weeks.Subsequently,they were assessed for morphology,bioelectrical properties,and gene expression related to oviduct function,glucocorticoid pathway,cortisol metabo-lism,inflammation,and apoptosis.Results revealed adverse effects of cortisol on epithelium structure,featured by deciliation,vacuole formation,and multilayering.Additionally,cortisol exposure led to an increase in transepithelial potential difference,downregulated mRNA expression of the major glucocorticoid receptor(NR3C1),upregulated the expression of cortisol-responsive genes(FKBP5,TSC22D3),and significant downregulation of oviductal glycopro-tein 1(OVGP1)and steroid receptors PGR and ESR1.The systematic comparison to a similar experiment previously performed by us in porcine oviduct epithelial cells,indicated that bovine cultures were more susceptible to elevated cortisol levels than porcine.The distinct responses between both species are likely linked to their divergence in the cortisol-induced expression changes of HSD11B2,an enzyme controlling the cellular capacity to metabolise cortisol.These findings provide insights into the species-specific reactions and reproductive consequences triggered by maternal stress.展开更多
Development of efficient and stable metal catalysts for the selective aqueous phase hydrodeoxygenation(HDO)of biomass-derived oxygenates to value-added biofuels is highly desired.An innovative surface microenvironment...Development of efficient and stable metal catalysts for the selective aqueous phase hydrodeoxygenation(HDO)of biomass-derived oxygenates to value-added biofuels is highly desired.An innovative surface microenvironment modulation strategy was used to construct the nitrogen-doped hollow carbon sphere encapsulated with Pd(Pd@NHCS-X,X:600–800)nanoreactors for catalytic HDO of biomass-derived vanillin in water.The specific surface microenvironments of Pd@NHCS catalysts including the electronic property of active Pd centers and the surface wettability and porous structure of NHCS supports could be well-controlled by the calcination temperature of catalysts.Intrinsic kinetic evaluations demonstrated that the Pd@NHCS-600 catalyst presented a high turnover frequency of 337.77 h^(–1)and a low apparent activation energy of 18.63 kJ/mol.The excellent catalytic HDO performance was attributed to the unique surface microenvironment of Pd@NHCS catalyst based on structure-performance relationship analysis and DFT calculations.It revealed that pyridinic N species dominated the electronic property regulation of Pd sites through electronic metal-support interaction(EMSI)and produced numerous electron-rich active Pd centers,which not only intensified the dissociation and activation of H2 molecules,but also substantially improved the activation capability of vanillin via the enhanced adsorption of–C=O group.The fine hydrophilicity and abundant porous structure promoted the uniform dispersion of catalyst and ensured the effective access of reactants to catalytic active centers in water.Additionally,the Pd@NHCS-600 catalyst exhibited excellent catalytic stability and broad substrate applicability for the selective aqueous phase HDO of various biomass-derived carbonyl compounds.The proposed surface microenvironment modulation strategy will provide a new consideration for the rational design of high-performance nitrogen-doped carbon-supported metal catalysts for catalytic biomass transformation.展开更多
Background:The centrosome,a crucial cellular structure involved in the mitotic process of eukaryotic cells,plays a significant role in tumor progression by regulating the growth and differentiation of neoplastic cells...Background:The centrosome,a crucial cellular structure involved in the mitotic process of eukaryotic cells,plays a significant role in tumor progression by regulating the growth and differentiation of neoplastic cells.This makes the centrosome a promising target for therapeutic strategies in cancer treatment.Methods:Utilizing data from the TCGA database,we identified centrosome-related genes and constructed a prognostic model for 518 lung adenocarcinoma patients.Prognosis-associated genes were initially screened using univariate Cox regression,with overfitting minimized by applying LASSO regression to remove collinearity.Finally,a set of 12 genes was selected through multivariable Cox regression for inclusion in the prognostic model.Results:The model’s performance was assessed using ROC curve analysis,demonstrating a robust predictive ability with an AUC of 0.728 in the training group and 0.695 in the validation group.Differential expression analysis between high-risk(HRLAs)and low-risk(LRLAs)individuals was performed,followed by enrichment analyses using KEGG,GO,Progeny,GSVA,and GSEA.These analyses revealed significant differences in immune-related pathways between the two groups.Immune microenvironment assessment through ssGSEA and ESTIMATE indicated that individuals with poor prognosis exhibited lower immune,stromal,and ESTIMATE scores,along with higher tumor purity,suggesting an impaired immune microenvironment in HRLAs patients.Drug susceptibility analysis and molecular docking showed that HRLAs individuals were more responsive to docetaxel,emphasizing the therapeutic relevance of paclitaxel in this cohort.Conclusion:We successfully developed and validated a centrosome-associated gene-based prognostic model,offering clinicians valuable insights for improved decision-making and personalized treatment strategies.This model may facilitate the identification of high-risk patients and guide therapeutic interventions in lung adenocarcinoma.展开更多
BACKGROUND The histone deacetylases 10(HDAC10)is a HDAC family member,yet its importance in the context of colorectal cancer(CRC)development remains incompletely understood.The present study was thus developed to expl...BACKGROUND The histone deacetylases 10(HDAC10)is a HDAC family member,yet its importance in the context of colorectal cancer(CRC)development remains incompletely understood.The present study was thus developed to explore the mechanistic importance of HDAC10 as a regulator of CRC.AIM To investigate the impact of HDAC10 on tumor growth and its regulation in tumor microenvironment(TME)in CRC,we conducted this study.METHODS The study evaluated HDAC10 expression using immunohistochemistry analyses and assessed its prognostic value in CRC patients.HDAC10 depletion CRC cell lines were generated,and its biological functions were assessed through cell counting kit-8,wound healing,and colony formation assays.Furthermore,gene set variation analysis(GSVA)was employed to explore the potential molecular mechanisms of HDAC10 in CRC.The impact of HDAC10 on TME was subsequently assessed.Finally,the study investigated the influence of HDAC10 on the response to immunotherapy and chemotherapeutic drugs in CRC.RESULTS HDAC10 expression was significantly elevated in CRC and correlated with poor prognosis in patients.Knockdown of HDAC10 reduced colon cancer cell proliferation and migration capabilities.GSVA revealed a strong association between high HDAC10 expression and immune suppression.Additionally,high HDAC10 levels were correlated with a non-inflamed TME.Finally,patients with high HDAC10 expression showed reduced sensitivity to immuno-therapy.CONCLUSION This study revealed the significance of HDAC10 in TME,therapy efficacy,and clinical prognosis in CRC,offering novel insights for therapeutic advancements in CRC.展开更多
Tumor stroma,or tumor microenvironment(TME),has been in the spotlight during recent years for its role in tumor development,growth,and metastasis.It consists of a myriad of elements,including tumor-associated macropha...Tumor stroma,or tumor microenvironment(TME),has been in the spotlight during recent years for its role in tumor development,growth,and metastasis.It consists of a myriad of elements,including tumor-associated macrophages,cancer-associated fibroblasts,a deregulated extracellular matrix,endothelial cells,and vascular vessels.The release of proinflammatory molecules,due to the inflamed microenvironment,such as cytokines and chemokines is found to play a pivotal role in progression of cancer and response to therapy.This review discusses the major key players and important chemical inflammatory signals released in the TME.Furthermore,the latest breakthroughs in cytokine-mediated crosstalk between immune cells and cancer cells have been highlighted.In addition,recent updates on alterations in cytokine signaling between chronic inflammation and malignant TME have also been reviewed.展开更多
Metabolic reprogramming is a prominent cancer hallmark that enables uncontrolled growth,survival,and dissemination of tumor cells.Among the diverse metabolic alterations,dysregulation of arginine metabolism has garner...Metabolic reprogramming is a prominent cancer hallmark that enables uncontrolled growth,survival,and dissemination of tumor cells.Among the diverse metabolic alterations,dysregulation of arginine metabolism has garnered significant attention due to its profound impact on cancer cells and the tumor microenvironment(TME).Arginine,a semi-essential amino acid,has a central role in various cellular processes,including protein synthesis,nitric oxide(NO)production,and polyamine biosynthesis.In the context of cancer aberrant arginine metabolism fuels tumor cell growth and orchestrates a complex interplay between tumor and immune cells,ultimately facilitating immune evasion and tumor progression.展开更多
BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related death globally,with the tumor immune microenvironment(TIME)influencing prognosis and immunotherapy response.Current TIME evaluation relies on invas...BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related death globally,with the tumor immune microenvironment(TIME)influencing prognosis and immunotherapy response.Current TIME evaluation relies on invasive biopsies,limiting its clinical application.This study hypothesized that computed tomography(CT)-based deep learning(DL)radiomics models can non-invasively predict key TIME biomarkers:Tumor-stroma ratio(TSR),tumor-infiltrating lymphocytes(TILs),and immune score(IS).AIM To develop a non-invasive DL approach using preoperative CT radiomics to evaluate TIME components in CRC patients.METHODS In this retrospective study,preoperative CT images of 315 pathologically confirmed CRC patients(220 in training cohort and 95 in validation cohort)were analyzed.Manually delineated regions of interest were used to extract DL features.Predictive models(DenseNet-121/169)for TSR,TILs,IS,and TIME classification were constructed.Performance was evaluated via receiver operating characteristic curves,calibration curves,and decision curve analysis(DCA).RESULTS The DL-DenseNet-169 model achieved area under the curve(AUC)values of 0.892[95%confidence interval(CI):0.828-0.957]for TSR and 0.772(95%CI:0.674-0.870)for TIME score.The DenseNet-121 model yielded AUC values of 0.851(95%CI:0.768-0.933)for TILs and 0.852(95%CI:0.775-0.928)for IS.Calibration curves demonstrated strong prediction-observation agreement,and DCA confirmed clinical utility across threshold probabilities(P<0.05 for all models).CONCLUSION CT-based DL radiomics provides a reliable non-invasive method for preoperative TIME evaluation,enabling personalized immunotherapy strategies in CRC management.展开更多
The tumor microenvironment(TME)plays a critical role in the development and treatment of liver cancer,which ranks sixth in incidence and third in mortality worldwide,according to the“Global Cancer Statistics 2022”.H...The tumor microenvironment(TME)plays a critical role in the development and treatment of liver cancer,which ranks sixth in incidence and third in mortality worldwide,according to the“Global Cancer Statistics 2022”.Hepatocellular carcinoma(HCC),the most common form of liver cancer,is heavily influenced by the TME,which affects tumor growth,invasion,metastasis,and the response to various treatments.Despite advancements in surgery,liver transplantation,targeted therapies,and immunotherapy,the complexity of the TME often limits treatment efficacy,especially in advanced-stage HCC cases.The TME consists of a dynamic interaction between tumor cells,immune cells,fibroblasts,blood vessels,and signaling molecules,all of which contribute to cancer progression and therapy resistance.Assessing the HCC TME is essential for designing effective,personalized treatments and improving patient outcomes.Recent research highlights the value of imaging technologies as non-invasive tools to evaluate the TME,offering new possibilities for more targeted therapies and better prognosis monitoring in HCC patients.展开更多
基金partially supported by grants from the Non-communicable Chronic Diseases-National Science and Technology Major Project(grant num-ber:2023ZD0510300)the National Natural Science Foundation of China(grant numbers:82403377,82473192).
文摘The landscape of tumor microenvironment(TME)research has un-dergone rapid transformation over the past decade.1,2 As we deepen our understanding of the TME’s role in cancer progression,immune response modulation,and therapeutic efficacy,this special issue,“Tumor Microen-vironment and Immunotherapy:From Bench to Bedside,”brings forth the latest breakthroughs in these domains.It highlights the interplay be-tween the TME,immune system dynamics,and cancer therapies,with a particular emphasis on precision medicine and the development of targeted treatments.
基金supported by the Natural Science Foundation of Hunan Province(No.2021JJ30589)Hunan Provincial Natural Science Foundation Sector Joint Fund(No.2023JJ60049).
文摘Approximately half of all cancers have p53 inactivating mutations,in addition to which most malignancies inactivate the p53 pathway by increasing p53 inhibitors,decreasing p53 activators,or inactivating p53 downstream targets.A growing number of researches have demonstrated that p53 can influence tumor progression through the tumor microenvironment(TME).TME is involved in the process of tumor development and metastasis and affects the clinical prognosis of patients.p53 participates in host immunity and engages in the immune landscape of the TME,but the specific mechanisms remain to be investigated.This review briefly explores the interactions between different states of p53 and TME components and their mechanisms,as well as their effects on tumor progression.To understand the progress of drug development and clinical studies related to p53 and tumor microenvironment.
基金Supported by the Shanghai Science and Technology Commission Project,No.21010504300Shanghai Jiading District Traditional Chinese Medicine Key Specialty Construction Project,No.2020-JDZYYZDZK-01.
文摘BACKGROUND In recent years,numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment(TIME).However,to date,no systematic study has been conducted on the relationship between gut microbiota and the TIME using bibliometric methods.AIM To describe the current global research status on the correlation between gut microbiota and the TIME,and to identify the most influential countries,research institutions,researchers,and research hotspots related to this topic.METHODS We searched for all literature related to gut microbiota and TIME published from January 1,2014,to May 28,2024,in the Web of Science Core Collection database.We then conducted a bibliometric analysis and created visual maps of the published literature on countries,institutions,authors,keywords,references,etc.,using CiteSpace(6.2R6),VOSviewer(1.6.20),and bibliometrics(based on R 4.3.2).RESULTS In total,491 documents were included,with a rapid increase in the number of publications starting in 2019.The country with the highest number of publications was China,followed by the United States.Germany has the highest number of citations in literature.From a centrality perspective,the United States has the highest influence in this field.The institutions with the highest number of publications were Shanghai Jiao Tong University and Zhejiang University.However,the institution with the most citations was the United States National Cancer Institute.Among authors,Professor Giorgio Trinchieri from the National Institutes of Health has the most local impact in this field.The most cited author was Fan XZ.The results of journal publications showed that the top three journals with the highest number of published papers were Frontiers in Immunology,Cancers,and Frontiers in Oncology.The three most frequently used keywords were gut microbiota,tumor microenvironment,and immunotherapy.CONCLUSION This study systematically elaborates on the research progress related to gut microbiota and TIME over the past decade.Research results indicate that the number of publications has rapidly increased since 2019,with research hotspots including“gut microbiota”,“tumor microenvironment”and“immunotherapy”.Exploring the effects of specific gut microbiota or derived metabolites on the behavior of immune cells in the TIME,regulating the secretion of immune molecules,and influencing immunotherapy are research hotspots and future research directions.
基金supported by the National Science Foundation of China(82202714).
文摘Severe tissue defects present formidable challenges to human health,persisting as major contributors to mortality rates.The complex pathological microenvironment,particularly the disrupted immune landscape within these defects,poses substantial hurdles to existing tissue regeneration strategies.However,the emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine,providing encouraging prospects for tissue regeneration and restoration.This review aims to gather recent advances in immunomodulatory nanomedicine to foster tissue regeneration.We begin by elucidating the distinctive features of the local immune microenvironment within defective tissues and its crucial role in tissue regeneration.Subsequently,we explore the design and functional properties of immunomodulatory nanosystems.Finally,we address the challenges and prospects of clinical translation in nanomedicine development,aiming to propose a potent approach to enhance tissue regeneration through synergistic immune modulation and nanomedicine integration.
基金financially supported by the Key Research and Development Program of Hubei Province(No.2022BCA082 and No.2022BEC013).
文摘The presence of impurities in phosphogypsum has long impeded its effective utilization,highlighting the need for energy-efficient and sustainable purification methods.This study proposes a novel purification strategy that synergistically combines pH regulation and micelle-assisted treatment to create an optimized microenvironment for impurity removal.Under mechanical grinding conditions,this approach enhances the rheological properties of the phosphogypsumslurries and facilitates the dissolution and removal of impurity ions.Experimental results demonstrate that the synergistic method achieves a remarkable 64.01%increase in whiteness while significantly reducing soluble phosphorus and fluoride content in a single-step process.This technique not only achieves high purification efficiency but also offers a practical pathway for the high-value utilization of phosphogypsum.These findings suggest that this method has substantial potential for enhancing sustainable resource management and enabling broader industrial applications of purified phosphogypsum.
基金supported by the National Natural Science Foundation of China(Nos.22078201,U1908202)Liaoning&Shenyang Key Laboratory of Functional Dye and Pigment(Nos.2021JH13/10200018,21-104-0-23,LJKZ0453)China Medical University’s High-Quality Development Science and Technology Funding Program(Nos.2022JH2/20200063,2023JH2/20200162).
文摘Therapy-induced modulation of the tumor microenvironment(TME)to overcome the immunosuppressive TME is considered to be a chance for cancer treatment.Herein,we prepared near-infrared absorbing aza-BODIPY PhEt-azaBDP with 1-phenylethyl group at 1,7-sites,a type I photodynamic-photothermal therapy(PDT-PTT)agent.Self-assembly PhEt-azaBDP nanoparticles(NPs)can provide combined phototherapeutic effects under light irradiation and simultaneously induce inflammatory TME,by monitoring tumorassociated macrophages(TAMs)repolarization.Utilizing cluster of differentiation 86(CD86)and CD163 as the M1-type marker and M2-type marker respectively,PhEt-azaBDP NPs resulted in the increasement of the expression of CD86 and the decreasement of the expression of CD163 in TAMs under near-infrared(NIR)light irradiation,promoting TAMs to switch from M2-phenotype to M1-phenotype.Inflammatory cytokines,interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α),could be the key cytokine involved in the phototherapy-induced TME reprogramming.PhEt-azaBDP NPs could be a potential theranostic scaffold for the simultaneous induction and detection of TME reprogramming triggered by phototherapy.
文摘Breast cancer is one of the most common malignancies worldwide and is a major cause of cancer-related mortality among women.Beyond tumor cells,the tumor microenvironment(TME)also plays an important role in cancer progression,therapy resistance,and metastasis.The TME is a complex ecosystem consisting of stromal and immune cells,extracellular matrix(ECM),and various signaling molecules that dynamically interact with tumor cells.Cancer-associated fibro-blasts remodel the ECM and secrete growth factors that promote tumor growth and invasion.Immune cells,such as tumor-associated macrophages,regulatory T cells,and myeloid-derived suppressor cells,often contribute to an immunosup-pressive environment that hinders anti-tumor immune responses.The ECM pro-vides structural support and acts as a reservoir for signaling molecules that in-fluence cancer cell behavior.These components evolve together with tumor cells,facilitating immune evasion,therapy resistance,and epithelial-to-mesenchymal transition,which promotes metastasis.Understanding these interactions is nece-ssary to develop novel therapeutic strategies that target both tumor and micro-environmental components.This minireview highlights the key stromal and immune elements within the breast cancer microenvironment,discussing their individual and collective roles in tumor progression and clinical outcomes,while emphasizing emerging therapeutic approaches aiming to reprogram the TME to improve treatment efficacy.
基金the financial support by National Natural Science Foundation of China(No.82171997)the Guangdong Basic and Applied Basic Research Fund Foundation(No.2023B1515120073)+2 种基金the Science and Technology Planning Project of Guangdong Province(No.2023B1212060013)Guangzhou Science and Technology Bureau(No.2023A03J0708)Shenzhen Science and Technology Program(Nos.JCYJ20230807111120043,JCYJ20220818102014028)。
文摘Sorafenib(Sora)not only has an inhibitory effect on angiogenesis via indirectly inhibiting tumor growth through antiangiogenesis,but also can inactivate the glutathione peroxidase 4(GPX4)to induce ferroptosis.Nonetheless,the therapeutic efficacy is hampered by a plethora of factors,including low bioavailability and tumor microenvironment(TME).Of particular note is the hypoxic and reductive TME,which acts as a significant impediment and poses formidable challenges to attain the most optimal treatment outcomes.Herein,we developed a novel therapeutic platform based on Sora-loaded mesoporous ferromanganese nanoparticles(PMFNs@Sora).PMFNs mimics both catalase and GPX activities.The self-sustained catalase activity enables continuous decomposition of hydrogen peroxide to generate oxygen,which alleviates hypoxia microenvironment.The GPX activity simultaneously amplifies the therapeutic efficacy of Sora.The as-synthesized PMFNs@Sora demonstrates significantly enhanced antitumor effect in vitro through apoptosis-ferroptosis,revealed by Western blot.Furthermore,PMFNs@Sora also showed effective tumor growth inhibition in vivo.This multifunctional nanoplatform offers a promising strategy for modulating the TME and enhancing cancer treatment in clinical application.
文摘The development of solid frustrated Lewis pairs(FLPs)catalysts with porous structures is a promising strategy for advancing green hydrogenation technologies and has garnered significant attention.Leveraging the diverse oxidation states and structural tunability of cerium-based metal-organic frameworks(Ce-MOFs),this study employed a competitive coordination strategy utilizing a single carboxylate functional group ligand to construct a series of MOF-808-X(X=-NH_(2),-OH,-Br,and-NO_(2))featuring rich solid-state FLPs for hydrogenation of unsaturated olefins.The-X functional group serves as a microenvironment,enhancing hydrogenation activity by modulating the electronic properties and acid-base characteristics of the FLP sites.The unique redox properties of elemental cerium facilitate the exposure of unsaturated Ce sites(Ce-CUS,Lewis acid(LA))and adjacent Ce-OH(Lewis base(LB))sites within the MOFs,generating abundant solid-state FLP(Ce-CUS/Ce-OH)sites.Experimental results demonstrate that Ce-CUS and Ce-OH interact with theσandσ^(*)orbitals of H-H,and this"push-pull"synergy promotes heterolytic cleavage of the H-H bond.The lone pair electrons of the electron-donating functional group are transmitted through the molecular backbone to the LB site,thereby increasing its strength and reducing the activation energy required for H_(2)heterolytic cleavage.Notably,at 100℃and 2 MPa H_(2),MOF-808-NH_(2)achieves complete conversion of styrene and dicyclopentadiene,significantly outperforming MOF-808.Based on in-situ analysis and density functional theory calculations,a plausible reaction mechanism is proposed.This research enriches the theoretical framework for unsaturated olefin hydrogenation catalysts and contributes to the development of efficient catalytic systems.
基金supported by grants from the National Natural Science Foundation of China(grant number:82170181)Beijing Natural Science Foundation(grant number:7222027)+4 种基金Beijing Physician Scientist Train-ing Project(grant number:BJPSTP-2024-01)the National Key R&D Program of China(grant number:2022YFF1502000)to Liang Wangthe National Key R&D Program of China(grant number:2022YFF1502000)Beijing Municipal Fund for Distinguished Young Scholars(grant number:JQ22022)to Lin FengHebei province government funding for clinical medical talents training and basic research projects(grant number:361007)to Youchao Jia.
文摘Background:Previous researches mainly focused on whether cancer stem cells exist in diffuse large B-cell lym-phoma(DLBCL).However,subgroups with dismal prognosis and stem cell-like characteristics have been over-looked.Methods:Using large scale data(n=2133),we conducted machine learning algorithms to identify a high risk DLBCL subgroup with stem cell-like features,and then investigated the potential mechanisms in shaping this subgroup using transcriptome,genome and single-cell RNA-seq data,and in vitro experiments.Results:We identified a high-risk subgroup(25.6%of DLBCL)with stem cell-like characteristics and dismal prog-nosis.This high-risk group(HRG)was featured by upregulation of key enzyme(ODC1)in polyamine metabolism and cold tumor microenvironment(TME),and had a poor prognosis with lower 3-year overall survival(OS)(54.3%vs.83.6%,P<0.0001)and progression-free survival(PFS)(42.8%vs.74.7%,P<0.0001)rates com-pared to the low-risk group.HRG also exhibited malignant proliferative phenotypes similar to Burkitt lymphoma.Patients with MYC rearrangement,double-hit,double-expressors,or complete remission might have either favor-able or poor prognosis,which could be further distinguished by our risk stratification model.Genomic analysis revealed widespread copy number losses in the chemokine and interferon coding regions 8p23.1 and 9p21.3 in HRG.We identified ODC1 as a therapeutic vulnerability for HRG-DLBCL.Single-cell analysis and in vitro ex-periments demonstrated that ODC1 overexpression enhanced DLBCL cell proliferation and drove macrophage polarization towards the M2 phenotype.Conversely,ODC1 inhibition reduced DLBCL cell proliferation,induced cell cycle arrest and apoptosis,and promoted macrophage polarization towards the M1 phenotype.Finally,we developed a comprehensive database of DLBCL for clinical application.Conclusions:Our study effectively advances the precise risk stratification of DLBCL and reveals that ODC1 and immune-deserted microenvironment jointly shape a group of DLBCL patients with stem cell-like features.Target-ing ODC1 regulates immunotherapies in DLBCL,offering new insights for DLBCL treatment.
基金supported by grants from National Natural Science Foundation of China(32370892)Science and Technology Commission of Shanghai Municipality(23141901200)+3 种基金Shanghai Natural Science Foundation(24ZR1450100)Health Commission of Shanghai Municipality(2022JC029)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiaotong University School of Medicine(2022LHA11)Talent-Introduction Program of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine(2022YJRC05).
文摘Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.
文摘Computed tomography-based deep learning radiomics provides a novel,noninvasive approach to predicting the tumor immune microenvironment in colorectal cancer,revolutionizing precision oncology.The retrospective study by Zhou et al analyzed preoperative computed tomography scans from 315 patients using convolutional neural networks,achieving robust predictive performance(area under the curve:0.851-0.892)for critical tumor immune microenvironment features,such as tumor-stroma ratio and lymphocyte infiltration,without requiring invasive biopsies.This editorial explores how this technique advances personalized immunotherapy,chemotherapy,and targeted therapies;challenges conventional oncology practices;and paves the way for a future of precision medicine.By integrating advanced imaging with immune profiling,deep learning radiomics redefines colorectal cancer management,highlighting the need to reevaluate the interplay of technology,biology,and ethics in gastrointestinal oncology.
基金German research Foundation(DFG,grant numbers:CH2321/1–1 and SCHO1231/7–1)JH has received a scholarship from the Chinese Scholarship Council(CSC No.:201908350115).
文摘The oviduct epithelium is the initial maternal contact site for embryos after fertilization,offering the microenviron-ment before implantation.This early gestation period is particularly sensitive to stress,which can cause reduced fertil-ity and reproductive disorders in mammals.Nevertheless,the local impact of elevated stress hormones on the ovi-duct epithelium has received limited attention to date,except for a few reports on polyovulatory species like mice and pigs.In this study,we focused on the effects of chronic maternal stress on cattle,given its association with infertil-ity issues in this monoovulatory species.Bovine oviduct epithelial cells(BOEC)differentiated at the air–liquid interface(ALI)were stimulated with 250 nmol/L cortisol for 1 or 3 weeks.Subsequently,they were assessed for morphology,bioelectrical properties,and gene expression related to oviduct function,glucocorticoid pathway,cortisol metabo-lism,inflammation,and apoptosis.Results revealed adverse effects of cortisol on epithelium structure,featured by deciliation,vacuole formation,and multilayering.Additionally,cortisol exposure led to an increase in transepithelial potential difference,downregulated mRNA expression of the major glucocorticoid receptor(NR3C1),upregulated the expression of cortisol-responsive genes(FKBP5,TSC22D3),and significant downregulation of oviductal glycopro-tein 1(OVGP1)and steroid receptors PGR and ESR1.The systematic comparison to a similar experiment previously performed by us in porcine oviduct epithelial cells,indicated that bovine cultures were more susceptible to elevated cortisol levels than porcine.The distinct responses between both species are likely linked to their divergence in the cortisol-induced expression changes of HSD11B2,an enzyme controlling the cellular capacity to metabolise cortisol.These findings provide insights into the species-specific reactions and reproductive consequences triggered by maternal stress.
文摘Development of efficient and stable metal catalysts for the selective aqueous phase hydrodeoxygenation(HDO)of biomass-derived oxygenates to value-added biofuels is highly desired.An innovative surface microenvironment modulation strategy was used to construct the nitrogen-doped hollow carbon sphere encapsulated with Pd(Pd@NHCS-X,X:600–800)nanoreactors for catalytic HDO of biomass-derived vanillin in water.The specific surface microenvironments of Pd@NHCS catalysts including the electronic property of active Pd centers and the surface wettability and porous structure of NHCS supports could be well-controlled by the calcination temperature of catalysts.Intrinsic kinetic evaluations demonstrated that the Pd@NHCS-600 catalyst presented a high turnover frequency of 337.77 h^(–1)and a low apparent activation energy of 18.63 kJ/mol.The excellent catalytic HDO performance was attributed to the unique surface microenvironment of Pd@NHCS catalyst based on structure-performance relationship analysis and DFT calculations.It revealed that pyridinic N species dominated the electronic property regulation of Pd sites through electronic metal-support interaction(EMSI)and produced numerous electron-rich active Pd centers,which not only intensified the dissociation and activation of H2 molecules,but also substantially improved the activation capability of vanillin via the enhanced adsorption of–C=O group.The fine hydrophilicity and abundant porous structure promoted the uniform dispersion of catalyst and ensured the effective access of reactants to catalytic active centers in water.Additionally,the Pd@NHCS-600 catalyst exhibited excellent catalytic stability and broad substrate applicability for the selective aqueous phase HDO of various biomass-derived carbonyl compounds.The proposed surface microenvironment modulation strategy will provide a new consideration for the rational design of high-performance nitrogen-doped carbon-supported metal catalysts for catalytic biomass transformation.
基金Key Research and Development Foundation supported by Science and Technology Department of Sichuan Province.Project Number:2023YFS0243Project Name:Application of Multiple Nucleic Acid Detection of Respiratory Pathogens Based on Multiple Fusion Curve Technology in Rapid Pathogenic Analysis of Acute Respiratory Distress Syndrome Patients Caused By Atypical Pathogen Infections in Emergency Departments+1 种基金Fund Name:Applied Basic Research Foundation supported by Science and Technology Department of Sichuan Province.Project Number:2021YJ0135Project Name:Explorating the Antiinflammatory Mechanism of Extracellular Vesicles Secreted by Wharton’s Jelly Mesenchymal Stem Cells in Alleviating Pulmonary Vascular Endothelial Injury and Discussing the Effectiveness of VEGF Gene Modification in Sepsis-related ALI/ARDS.
文摘Background:The centrosome,a crucial cellular structure involved in the mitotic process of eukaryotic cells,plays a significant role in tumor progression by regulating the growth and differentiation of neoplastic cells.This makes the centrosome a promising target for therapeutic strategies in cancer treatment.Methods:Utilizing data from the TCGA database,we identified centrosome-related genes and constructed a prognostic model for 518 lung adenocarcinoma patients.Prognosis-associated genes were initially screened using univariate Cox regression,with overfitting minimized by applying LASSO regression to remove collinearity.Finally,a set of 12 genes was selected through multivariable Cox regression for inclusion in the prognostic model.Results:The model’s performance was assessed using ROC curve analysis,demonstrating a robust predictive ability with an AUC of 0.728 in the training group and 0.695 in the validation group.Differential expression analysis between high-risk(HRLAs)and low-risk(LRLAs)individuals was performed,followed by enrichment analyses using KEGG,GO,Progeny,GSVA,and GSEA.These analyses revealed significant differences in immune-related pathways between the two groups.Immune microenvironment assessment through ssGSEA and ESTIMATE indicated that individuals with poor prognosis exhibited lower immune,stromal,and ESTIMATE scores,along with higher tumor purity,suggesting an impaired immune microenvironment in HRLAs patients.Drug susceptibility analysis and molecular docking showed that HRLAs individuals were more responsive to docetaxel,emphasizing the therapeutic relevance of paclitaxel in this cohort.Conclusion:We successfully developed and validated a centrosome-associated gene-based prognostic model,offering clinicians valuable insights for improved decision-making and personalized treatment strategies.This model may facilitate the identification of high-risk patients and guide therapeutic interventions in lung adenocarcinoma.
基金Supported by National Natural Science Foundation of China,No.82403279 and No.82303181.
文摘BACKGROUND The histone deacetylases 10(HDAC10)is a HDAC family member,yet its importance in the context of colorectal cancer(CRC)development remains incompletely understood.The present study was thus developed to explore the mechanistic importance of HDAC10 as a regulator of CRC.AIM To investigate the impact of HDAC10 on tumor growth and its regulation in tumor microenvironment(TME)in CRC,we conducted this study.METHODS The study evaluated HDAC10 expression using immunohistochemistry analyses and assessed its prognostic value in CRC patients.HDAC10 depletion CRC cell lines were generated,and its biological functions were assessed through cell counting kit-8,wound healing,and colony formation assays.Furthermore,gene set variation analysis(GSVA)was employed to explore the potential molecular mechanisms of HDAC10 in CRC.The impact of HDAC10 on TME was subsequently assessed.Finally,the study investigated the influence of HDAC10 on the response to immunotherapy and chemotherapeutic drugs in CRC.RESULTS HDAC10 expression was significantly elevated in CRC and correlated with poor prognosis in patients.Knockdown of HDAC10 reduced colon cancer cell proliferation and migration capabilities.GSVA revealed a strong association between high HDAC10 expression and immune suppression.Additionally,high HDAC10 levels were correlated with a non-inflamed TME.Finally,patients with high HDAC10 expression showed reduced sensitivity to immuno-therapy.CONCLUSION This study revealed the significance of HDAC10 in TME,therapy efficacy,and clinical prognosis in CRC,offering novel insights for therapeutic advancements in CRC.
文摘Tumor stroma,or tumor microenvironment(TME),has been in the spotlight during recent years for its role in tumor development,growth,and metastasis.It consists of a myriad of elements,including tumor-associated macrophages,cancer-associated fibroblasts,a deregulated extracellular matrix,endothelial cells,and vascular vessels.The release of proinflammatory molecules,due to the inflamed microenvironment,such as cytokines and chemokines is found to play a pivotal role in progression of cancer and response to therapy.This review discusses the major key players and important chemical inflammatory signals released in the TME.Furthermore,the latest breakthroughs in cytokine-mediated crosstalk between immune cells and cancer cells have been highlighted.In addition,recent updates on alterations in cytokine signaling between chronic inflammation and malignant TME have also been reviewed.
基金supported by grants from the National Key R&D Program of China(Grant no.2022YFC3401001)the National Natural Science Foundation of China(Grant nos.82025026,82230091,and 81872144)the Guangdong Basic and Applied Basic Research Foundation(Grant no.2023A1515140033).
文摘Metabolic reprogramming is a prominent cancer hallmark that enables uncontrolled growth,survival,and dissemination of tumor cells.Among the diverse metabolic alterations,dysregulation of arginine metabolism has garnered significant attention due to its profound impact on cancer cells and the tumor microenvironment(TME).Arginine,a semi-essential amino acid,has a central role in various cellular processes,including protein synthesis,nitric oxide(NO)production,and polyamine biosynthesis.In the context of cancer aberrant arginine metabolism fuels tumor cell growth and orchestrates a complex interplay between tumor and immune cells,ultimately facilitating immune evasion and tumor progression.
基金Supported by the National Natural Science Foundation of China,No.81860047the Natural Science Foundation of Gansu Province,No.22JR5RA650+1 种基金Key Science and Technology Program in Gansu Province,No.21YF5FA016Gansu Provincial Hospital Scientific Research Foundation,No.23GSSYD-12.
文摘BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related death globally,with the tumor immune microenvironment(TIME)influencing prognosis and immunotherapy response.Current TIME evaluation relies on invasive biopsies,limiting its clinical application.This study hypothesized that computed tomography(CT)-based deep learning(DL)radiomics models can non-invasively predict key TIME biomarkers:Tumor-stroma ratio(TSR),tumor-infiltrating lymphocytes(TILs),and immune score(IS).AIM To develop a non-invasive DL approach using preoperative CT radiomics to evaluate TIME components in CRC patients.METHODS In this retrospective study,preoperative CT images of 315 pathologically confirmed CRC patients(220 in training cohort and 95 in validation cohort)were analyzed.Manually delineated regions of interest were used to extract DL features.Predictive models(DenseNet-121/169)for TSR,TILs,IS,and TIME classification were constructed.Performance was evaluated via receiver operating characteristic curves,calibration curves,and decision curve analysis(DCA).RESULTS The DL-DenseNet-169 model achieved area under the curve(AUC)values of 0.892[95%confidence interval(CI):0.828-0.957]for TSR and 0.772(95%CI:0.674-0.870)for TIME score.The DenseNet-121 model yielded AUC values of 0.851(95%CI:0.768-0.933)for TILs and 0.852(95%CI:0.775-0.928)for IS.Calibration curves demonstrated strong prediction-observation agreement,and DCA confirmed clinical utility across threshold probabilities(P<0.05 for all models).CONCLUSION CT-based DL radiomics provides a reliable non-invasive method for preoperative TIME evaluation,enabling personalized immunotherapy strategies in CRC management.
基金Supported by the National Natural Science Foundation of China,No.82360132the First Hospital of Lanzhou University,No.ldyyyn2020-14.
文摘The tumor microenvironment(TME)plays a critical role in the development and treatment of liver cancer,which ranks sixth in incidence and third in mortality worldwide,according to the“Global Cancer Statistics 2022”.Hepatocellular carcinoma(HCC),the most common form of liver cancer,is heavily influenced by the TME,which affects tumor growth,invasion,metastasis,and the response to various treatments.Despite advancements in surgery,liver transplantation,targeted therapies,and immunotherapy,the complexity of the TME often limits treatment efficacy,especially in advanced-stage HCC cases.The TME consists of a dynamic interaction between tumor cells,immune cells,fibroblasts,blood vessels,and signaling molecules,all of which contribute to cancer progression and therapy resistance.Assessing the HCC TME is essential for designing effective,personalized treatments and improving patient outcomes.Recent research highlights the value of imaging technologies as non-invasive tools to evaluate the TME,offering new possibilities for more targeted therapies and better prognosis monitoring in HCC patients.
