In a series of experiments,Phelps et al.1provided novel data linking moderate-to-vigorous physical activity (MVPA),gut microbiota composition changes and the release of the short chain fatty acid (SCFA) formate,and en...In a series of experiments,Phelps et al.1provided novel data linking moderate-to-vigorous physical activity (MVPA),gut microbiota composition changes and the release of the short chain fatty acid (SCFA) formate,and enhanced antitumor immunity via the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in cytotoxic CD8+T cells.These data support the growing awareness that the clinical benefits of MVPA are achieved at least in part through enhanced immunity with support from the gut microbiome.展开更多
Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune check...Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune checkpoint-T cell”axis.Collagen not only constitutes a mechanical barrier that distinguishes between the periphery and core of solid tumors but also systematically remodels the orientation of metabolism,vasculature,and immune cell phenotypic plasticity through its spatial density,fiber arrangement,and crosslinking patterns(F igure 1)[1,2].Abundant evidence suggests that over-accumulated types I and III collagen drive CD8+T cell exhaustion,NK cell functional inhibition,and tumor-associated macrophage polarization through ligand-receptor networks involving LAIR-1,DDR2,andβ1/β3 integrins[3-6].Mechanistically,collagen engagement of LAIR-1 delivers inhibitory signals in effector lymphocytes,promoting dysfunctional or exhausted states[7-9].In parallel,collagen-β1/β3 integrin signaling activates mechanotransduction pathways(e.g.,FAK/SRC),reducing T-cell motility and immune-tumor contact,while DDR2 activation supports matrix-remodeling programs that limit lymphocyte trafficking.展开更多
Objectives:Immunotherapy based on immune checkpoint blockade(ICB)has become a key treatment for melanoma.However,the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop met...Objectives:Immunotherapy based on immune checkpoint blockade(ICB)has become a key treatment for melanoma.However,the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop methods to overcome this resistance.This study aims to collect the most recent information on melanoma immunotherapy,discuss potential strategies to overcome resistance to immunotherapy,and identify areas that require further analysis.Methods:To achieve this goal,scientific publications from 2021-2024 available in PubMed and Google Scholar databases were analyzed.The databases were searched using the following terms:“melanoma”,“immunotherapy”,“Immune Checkpoint Blockade”,and“immunoresistance”.Results:The results of preclinical and early-stage clinical research indicate the potential application of tank-binding kinase 1(TBK-1),fecal microbiota transplant(FMT),Toll-like Receptor 9(TLR9),lipid nanoparticles(LNPs)containing a stimulator of an interferon gene agonist(STING),BRAF inhibitors,Lymphocyte Activation Gene(LAG-3),T-Cell Immunoglobulin and ITIM Domain(TIGIT),and oncolytic viruses(OVs)as potential methods to enhance melanoma sensitivity to ICB.Discussion:To optimize immunotherapy,further research is needed to determine the detailed mechanisms of action,safety profiles,tolerability,and precise patient selection criteria for methods capable of overcoming melanoma’s immunoresistance.展开更多
Highly potent chemotherapy provides rapid therapeutic efficacy in melanoma, but is often limited by drug resistance, off-target toxicity, and systemic toxicity. Combination therapy with chemotherapy and immunotherapy ...Highly potent chemotherapy provides rapid therapeutic efficacy in melanoma, but is often limited by drug resistance, off-target toxicity, and systemic toxicity. Combination therapy with chemotherapy and immunotherapy has attracted much attention but still faces challenges such as inconsistent immune responses and systemic toxicity. To address these limitations, we developed cathepsin B-activatable doxorubicin(DOX) prodrug nanoparticles(Cat B-NPs) for inducing tumor-specific immunogenic cell death(ICD), while minimizing off-target toxicity in normal tissues with low cathepsin B expression. The cathepsin Bactivatable DOX prodrug was synthesized by conjugating the cathepsin B-cleavable peptide(FRRL) to DOX, yielding FRRL-DOX. The amphiphilic FRRL-DOX formed stable nanoparticles(163.6 ± 13.5 nm) through intermolecular hydrophobic interaction and π-π stacking. In melanoma cells overexpressing cathepsin B, Cat B-NPs effectively induced cancer cellspecific ICD, while sparing normal cells and immune cells. When Cat B-NPs-treated B16F10cells were co-cultured with immune cells, Cat B-NPs enhanced the phagocytic activity of macrophages and induced the maturation of dendritic cells(DCs). In melanoma models,Cat B-NPs passively accumulated at tumor tissues through the enhanced permeability and retention effect and were selectively activated by intratumoral cathepsin B, enabling highdose treatment that induced robust ICD. Importantly, combination therapy with Cat B-NPs and anti-PD-L1 antibody enhanced ICD, DC maturation and T-cell activation, resulting in complete tumor regression in 50% of treated mice by converting the immunosuppressive tumor environment into an immune-responsive state. In a lung metastasis model, highdose Cat B-NPs with anti-PD-L1 also suppressed metastatic burden without systemic toxicity, supporting their potential as a safe and effective chemo-immunotherapy for melanoma.展开更多
Microglia cells are the resident innate immune cells of the central nervous system(CNS)(Paolicelli et al.,2022).They play a pivotal role in CNS development and in maintaining homeostasis during adulthood.Microglia are...Microglia cells are the resident innate immune cells of the central nervous system(CNS)(Paolicelli et al.,2022).They play a pivotal role in CNS development and in maintaining homeostasis during adulthood.Microglia are being extensively studied for their involvement in CNS disorders,ranging from autoimmune diseases such as multiple sclerosis to neurodegenerative and psychiatric conditions,as well as stroke and brain tumors(Paolicelli et al.,2022).展开更多
Current immunological research covers a broad spectrum of areas,including host defense mechanisms,inflammatory signaling pathways,immune regulation,immunometabolism,and therapeutic interventions,with an increasing foc...Current immunological research covers a broad spectrum of areas,including host defense mechanisms,inflammatory signaling pathways,immune regulation,immunometabolism,and therapeutic interventions,with an increasing focus on systems immunology and multi-omics,nextgeneration cell therapies and biologics,and disease microenvironment analyses.This special issue comprises one review,eight original articles,and a letter covering diverse topics,including opioidmediated immunomodulation,wound healing,osteoarthritis pathogenesis,neutrophil extracellular trap formation,vector control strategies,the genetic basis of the gut-skin axis,hepatitis C vaccine development,single-cell immune profiling in viral infection,neutralizing antibody discovery,and the association between vitamin D levels and cancer risk in psoriasis patients.展开更多
Despite effective antiretroviral therapy(ART),many individuals with human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(AIDS)achieve viral suppression but fail to fully restore cluster of differentia...Despite effective antiretroviral therapy(ART),many individuals with human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(AIDS)achieve viral suppression but fail to fully restore cluster of differentiation 4(CD4)^(+)T lymphocyte(CD4 cell)counts—a condition known as immunological non-response(INRs).INRs are associated with elevated health risks,including increased susceptibility to AIDS-related and non-AIDS-related complications.The pathogenesis of INRs remains incompletely understood,and no established therapeutic interventions exist,posing a major challenge in contemporary HIV/AIDS management.Emerging evidence indicates that INRs exhibit significant alterations in gut microbiota composition.Dysbiosis of the gut microbiota may contribute to persistent immune activation,cytokine imbalance,and cellular pyroptosis,all of which could impair immune reconstitution in people living with HIV/AIDS.Traditional Chinese medicine(TCM)has demonstrated potential immunomodulatory effects and is increasingly utilized in the management of INRs.Targeting the gut microbiota and elucidating the mechanisms by which TCM modulates this microbial ecosystem may offer new avenues for preventing and treating INRs.This review explores the interplay between gut microbiota and TCM,examines the association between gut dysbiosis and INRs,discusses the mechanistic pathways through which microbiota imbalance contributes to INRs development,and highlights how TCM interventions regulate gut microbiota to promote immune recovery.By focusing on the gut microbiota as a therapeutic interface,this article provides novel insights into TCM-based strategies for improving outcomes in INRs and supports the development of innovative treatment approaches.展开更多
Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and ...Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and osteoclast activity.However,the majority of research to date has focused on the direct effects of peripheral nerves and their neurotransmitters on bone regeneration.Emerging studies have begun to reveal a more intricate role of nerves in regulating the immune microenvironment,which is crucial for bone regeneration.This review summarizes how nerves influence bone regeneration through modulation of the immune microenvironment.We first discuss the changes in peripheral nerves during the regenerative process.We then describe conduction and paracrine pathways through which nerves affect the osteogenic immune microenvironment,emphasizing nerves,neural factors,and their impacts.Our goal is to deepen the understanding of the nerve-immune axis in bone regeneration.A better grasp of how nerves influence the osteogenic immune microenvironment may lead to new strategies that integrate the nervous,immune,and skeletal systems to promote bone regeneration.展开更多
Probiotics can regulate the body’s immune system through both non-specific and specific immunity,thereby regulating host health.In terms of non-specific immune regulation,probiotics can activate the intrinsic immune ...Probiotics can regulate the body’s immune system through both non-specific and specific immunity,thereby regulating host health.In terms of non-specific immune regulation,probiotics can activate the intrinsic immune system,regulate the mucosal barrier function,and play an immune role by influencing the activity of intrinsic immune cells such as macrophages,dendritic cells and natural killer cells,as well as their differentiation and maturation;in terms of specific immune regulation,probiotics play a role in regulating the immunoglobulin level and the maturation of B cells.Probiotics can also regulate T-cell differentiation according to the condition of the body,thus regulating specific immunity.Many studies have focused on the role of probiotics in metabolism and nutrition,and the mechanisms involved in the immunomodulatory role of probiotics have only been partially described.This review summarises the role of common probiotics such as Lactobacillus plantarum and Lactobacillus rhamnosus in immunomodulation as well as their mechanisms,describing the currently known mechanisms of immunomodulation by probiotics in improving the host immune system.A deeper understanding of probiotics and their specific mechanisms of action will facilitate the use of probiotics for immunomodulation in clinical medicine,functional foods,and other areas.This will also contribute to the development and research of engineered probiotics,next-generation probiotics,and other new functional probiotics with immunomodulatory effects.展开更多
Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immun...Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.展开更多
Amyotrophic lateral sclerosis is characterized by the progressive loss of motor neurons.Early-stage axonal dysfunction,rather than central nervous system injury,plays a key role in the disease process.However,the mole...Amyotrophic lateral sclerosis is characterized by the progressive loss of motor neurons.Early-stage axonal dysfunction,rather than central nervous system injury,plays a key role in the disease process.However,the molecular mechanisms underlying this dysfunction remain unclear.To investigate the relationship between peripheral immune dysregulation and axonal dysfunction in amyotrophic lateral sclerosis,we recruited 372 patients within the first 12 months of sporadic amyotrophic lateral sclerosis onset between January 2018 and May 2024.We collected peripheral immune markers at baseline,including total leukocytes,lymphocytes,monocytes,neutrophils,basophils,eosinophils,and platelets.We also calculated four derived ratios:neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,lymphocyte-to-monocyte ratio,and systemic immune inflammation index.Multivariate analysis,adjusted for confounding factors,revealed that higher counts of total leukocytes and neutrophils,as well as higher neutrophil-related ratios,including the neutrophil to lymphocyte ratio and the systemic immune inflammation index,were significantly correlated with higher compound muscle action potential scores.Stratified analyses revealed that these associations varied by age and sex.Furthermore,mediation analysis demonstrated that axonal dysfunction plays a significant role in the relationship between immune markers and disease progression.These findings emphasize the critical role that peripheral immune dysregulation plays in amyotrophic lateral sclerosis progression by mediating peripheral nerve injury,particularly in the early stages of the disease.This study highlights the importance of the peripheral nervous system in the early stages of amyotrophic lateral sclerosis and provides new insights into disease mechanisms and potential therapeutic targets.展开更多
Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regula...Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.展开更多
Objective:To analyze the efficacy of allergen subcutaneous injection immunotherapy in patients with allergic rhinitis.Methods:Fifty patients with allergic rhinitis admitted from May 2023 to May 2025 were selected as s...Objective:To analyze the efficacy of allergen subcutaneous injection immunotherapy in patients with allergic rhinitis.Methods:Fifty patients with allergic rhinitis admitted from May 2023 to May 2025 were selected as study subjects and randomly divided into a control group and an observation group,with 25 patients in each group.The control group was treated with budesonide nasal spray,while the observation group received allergen subcutaneous injection immunotherapy in addition to the control treatment.The treatment efficacy,adverse reactions,symptom improvement time,and immune indicators were compared between the two groups.Results:The observation group showed a higher disease treatment efficacy than the control group(p<0.05);the incidence of adverse reactions in the observation group was not statistically significant compared to the control group(p>0.05);the observation group had a shorter symptom improvement time for nasal obstruction,rhinorrhea,and sneezing than the control group(p<0.05);before treatment,there was no statistical significance in immune indicators between the two groups(p>0.05);after treatment,CD3+and CD4/CD8+in the observation group were higher than those in the control group(p<0.05).Conclusion:Allergen subcutaneous injection immunotherapy in patients with allergic rhinitis can improve disease treatment efficacy,alleviate clinical symptoms,and enhance immune function.This therapy is safe and has clinical application value.展开更多
Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the...Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.展开更多
Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated ...Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.展开更多
The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer’s disease.Microglia are resident immune cells in the brain that may orchestrate communication between the centra...The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer’s disease.Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system,though the mechanisms are unclear.Here,we found that gamma-type immunoglobulin,a product originating from peripheral blood B cells,localized in the brain parenchyma of multiple mouse models with amyloid pathology,and was enriched on microglia but not on other brain cell types.Further experiments showed that gamma-type immunoglobulin bound to microglial cell membranes and led to diverse transcriptomic changes,including upregulation of pathways related to phagocytosis and immunity.Functional assays demonstrated that gamma-type immunoglobulin enhanced microglial phagocytic capacity for amyloid-beta fibrils via its Fc fragment,but not Fab fragment,fragment.Our data indicate that microglia,when exposed to gamma-type immunoglobulin,exhibit an enhanced capacity for clearing amyloid-beta fibrils,potentially via the gamma-type immunoglobulin Fc fragment signaling pathway.This suggests that parenchymal gamma-type immunoglobulin should be further investigated to determine whether it may play a beneficial role against Alzheimer’s disease by enhancing microglial function.展开更多
Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of mul...Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.展开更多
Glioblastoma(GBM),the most aggressive and lethal primary brain tumor in adults,continues to resist conventional therapeutic approaches,withmedian survival remaining dismally low.Immune checkpoint inhibitors(ICIs),whic...Glioblastoma(GBM),the most aggressive and lethal primary brain tumor in adults,continues to resist conventional therapeutic approaches,withmedian survival remaining dismally low.Immune checkpoint inhibitors(ICIs),which have revolutionized the treatment of several solid tumors,have shown limited efficacy inGBMowing to the highly immunosuppressive and heterogeneousmicroenvironment of the tumor.The unique immune landscape of the central nervous system(CNS),characterized by low immunogenicity,restricted T-cell infiltration,and an abundance of regulatory and myeloid-derived suppressor cells,poses considerable barriers to effective immune reactivation.This review provides a comprehensive synthesis of the mechanistic barriers undermining ICI efficacy in GBM,including the blood-brain barrier,low tumor mutational burden,adaptive immune resistance,and iatrogenic immunosuppression.It also explores emerging predictive and prognostic biomarkers,such as programmed death-ligand 1(PD-L1)expression,immune gene signatures,tumor-infiltrating lymphocyte profiles,and circulating markers in cerebrospinal fluid and plasma,which hold promise for guiding patient selection and therapeutic monitoring.Importantly,recent breakthroughs in combinatorial immunotherapy strategies are highlighted,including the integration of ICIs with radiotherapy,anti-angiogenic agents,oncolytic viruses,personalized neoantigen vaccines,and tumor microenvironment reprogramming approaches.Innovative delivery platforms,such as nanoparticles,focused ultrasound,and convection-enhanced delivery,are also discussed for their potential to improve drug bioavailability and local immune activation in the CNS.This review hypothesizes that the therapeutic efficacy of ICIs in GBM can be considerably enhanced by disrupting immune exclusion and reversing immunosuppression through integrated,multimodal strategies guided by dynamic biomarker profiling and spatially resolved immunemapping.This hypothesisdriven approach aims to bridge translational gaps and inform next-generation clinical trial designs that may unlock the potential of immunotherapy for GBM.展开更多
Liver diseases are of growing interest to clinicians and researchers due to their high prevalence,difficulty in early diagnosis,and limited treatment options.The liver is an important organ at the intersection of many...Liver diseases are of growing interest to clinicians and researchers due to their high prevalence,difficulty in early diagnosis,and limited treatment options.The liver is an important organ at the intersection of many metabolic and immune pathways.To this end,it contains a large number of immune cells of both the innate and adaptive immune system that perform multiple functions,detecting and destroying pathogens that enter the body through the intestine,as well as recognizing endogenous antigens.Immune cells in the liver have a complex regulation that can be impaired in various diseases such as metabolic dysfunctionassociated steatotic liver disease(MASLD),liver cancer,and biliary diseases.A growing body of evidence reinforces the realization that not only impaired metabolism but also many immune mechanisms underlie MASLD.The liver has complex bilateral immune and metabolic links with the gut microbiota,and disruptions of these links underlie the development and progression of both gastrointestinal and other organ diseases.In this regard,acting on immune mechanisms is a promising therapeutic target for liver diseases.展开更多
Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor i...Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified;some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration(FDA) for clinical treatment. However, limited responses and immune-related adverse events(ir AEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.展开更多
文摘In a series of experiments,Phelps et al.1provided novel data linking moderate-to-vigorous physical activity (MVPA),gut microbiota composition changes and the release of the short chain fatty acid (SCFA) formate,and enhanced antitumor immunity via the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in cytotoxic CD8+T cells.These data support the growing awareness that the clinical benefits of MVPA are achieved at least in part through enhanced immunity with support from the gut microbiome.
基金supported by the National Natural Science Foundation of China(82472842 and 82473350)and Wuxi Double-Hundred Talent Fund Project(BJ2023075).
文摘Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune checkpoint-T cell”axis.Collagen not only constitutes a mechanical barrier that distinguishes between the periphery and core of solid tumors but also systematically remodels the orientation of metabolism,vasculature,and immune cell phenotypic plasticity through its spatial density,fiber arrangement,and crosslinking patterns(F igure 1)[1,2].Abundant evidence suggests that over-accumulated types I and III collagen drive CD8+T cell exhaustion,NK cell functional inhibition,and tumor-associated macrophage polarization through ligand-receptor networks involving LAIR-1,DDR2,andβ1/β3 integrins[3-6].Mechanistically,collagen engagement of LAIR-1 delivers inhibitory signals in effector lymphocytes,promoting dysfunctional or exhausted states[7-9].In parallel,collagen-β1/β3 integrin signaling activates mechanotransduction pathways(e.g.,FAK/SRC),reducing T-cell motility and immune-tumor contact,while DDR2 activation supports matrix-remodeling programs that limit lymphocyte trafficking.
文摘Objectives:Immunotherapy based on immune checkpoint blockade(ICB)has become a key treatment for melanoma.However,the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop methods to overcome this resistance.This study aims to collect the most recent information on melanoma immunotherapy,discuss potential strategies to overcome resistance to immunotherapy,and identify areas that require further analysis.Methods:To achieve this goal,scientific publications from 2021-2024 available in PubMed and Google Scholar databases were analyzed.The databases were searched using the following terms:“melanoma”,“immunotherapy”,“Immune Checkpoint Blockade”,and“immunoresistance”.Results:The results of preclinical and early-stage clinical research indicate the potential application of tank-binding kinase 1(TBK-1),fecal microbiota transplant(FMT),Toll-like Receptor 9(TLR9),lipid nanoparticles(LNPs)containing a stimulator of an interferon gene agonist(STING),BRAF inhibitors,Lymphocyte Activation Gene(LAG-3),T-Cell Immunoglobulin and ITIM Domain(TIGIT),and oncolytic viruses(OVs)as potential methods to enhance melanoma sensitivity to ICB.Discussion:To optimize immunotherapy,further research is needed to determine the detailed mechanisms of action,safety profiles,tolerability,and precise patient selection criteria for methods capable of overcoming melanoma’s immunoresistance.
基金supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)(RS-2024-00351185, RS-2025-02219039)by the Korea Health Industry Development Institute (KHIDI)grant funded by the Korea government (MOHW)(RS-2023-KH135133)by Korea Drug Development Fund (KDDF)funded by Ministry of Science and ICT,Ministry of Trade,Industry,and Energy,and Ministry of Health and Welfare(RS-2025-02223093)。
文摘Highly potent chemotherapy provides rapid therapeutic efficacy in melanoma, but is often limited by drug resistance, off-target toxicity, and systemic toxicity. Combination therapy with chemotherapy and immunotherapy has attracted much attention but still faces challenges such as inconsistent immune responses and systemic toxicity. To address these limitations, we developed cathepsin B-activatable doxorubicin(DOX) prodrug nanoparticles(Cat B-NPs) for inducing tumor-specific immunogenic cell death(ICD), while minimizing off-target toxicity in normal tissues with low cathepsin B expression. The cathepsin Bactivatable DOX prodrug was synthesized by conjugating the cathepsin B-cleavable peptide(FRRL) to DOX, yielding FRRL-DOX. The amphiphilic FRRL-DOX formed stable nanoparticles(163.6 ± 13.5 nm) through intermolecular hydrophobic interaction and π-π stacking. In melanoma cells overexpressing cathepsin B, Cat B-NPs effectively induced cancer cellspecific ICD, while sparing normal cells and immune cells. When Cat B-NPs-treated B16F10cells were co-cultured with immune cells, Cat B-NPs enhanced the phagocytic activity of macrophages and induced the maturation of dendritic cells(DCs). In melanoma models,Cat B-NPs passively accumulated at tumor tissues through the enhanced permeability and retention effect and were selectively activated by intratumoral cathepsin B, enabling highdose treatment that induced robust ICD. Importantly, combination therapy with Cat B-NPs and anti-PD-L1 antibody enhanced ICD, DC maturation and T-cell activation, resulting in complete tumor regression in 50% of treated mice by converting the immunosuppressive tumor environment into an immune-responsive state. In a lung metastasis model, highdose Cat B-NPs with anti-PD-L1 also suppressed metastatic burden without systemic toxicity, supporting their potential as a safe and effective chemo-immunotherapy for melanoma.
文摘Microglia cells are the resident innate immune cells of the central nervous system(CNS)(Paolicelli et al.,2022).They play a pivotal role in CNS development and in maintaining homeostasis during adulthood.Microglia are being extensively studied for their involvement in CNS disorders,ranging from autoimmune diseases such as multiple sclerosis to neurodegenerative and psychiatric conditions,as well as stroke and brain tumors(Paolicelli et al.,2022).
文摘Current immunological research covers a broad spectrum of areas,including host defense mechanisms,inflammatory signaling pathways,immune regulation,immunometabolism,and therapeutic interventions,with an increasing focus on systems immunology and multi-omics,nextgeneration cell therapies and biologics,and disease microenvironment analyses.This special issue comprises one review,eight original articles,and a letter covering diverse topics,including opioidmediated immunomodulation,wound healing,osteoarthritis pathogenesis,neutrophil extracellular trap formation,vector control strategies,the genetic basis of the gut-skin axis,hepatitis C vaccine development,single-cell immune profiling in viral infection,neutralizing antibody discovery,and the association between vitamin D levels and cancer risk in psoriasis patients.
基金supported by the National Natural Science Foundation of China(No.82274474)。
文摘Despite effective antiretroviral therapy(ART),many individuals with human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(AIDS)achieve viral suppression but fail to fully restore cluster of differentiation 4(CD4)^(+)T lymphocyte(CD4 cell)counts—a condition known as immunological non-response(INRs).INRs are associated with elevated health risks,including increased susceptibility to AIDS-related and non-AIDS-related complications.The pathogenesis of INRs remains incompletely understood,and no established therapeutic interventions exist,posing a major challenge in contemporary HIV/AIDS management.Emerging evidence indicates that INRs exhibit significant alterations in gut microbiota composition.Dysbiosis of the gut microbiota may contribute to persistent immune activation,cytokine imbalance,and cellular pyroptosis,all of which could impair immune reconstitution in people living with HIV/AIDS.Traditional Chinese medicine(TCM)has demonstrated potential immunomodulatory effects and is increasingly utilized in the management of INRs.Targeting the gut microbiota and elucidating the mechanisms by which TCM modulates this microbial ecosystem may offer new avenues for preventing and treating INRs.This review explores the interplay between gut microbiota and TCM,examines the association between gut dysbiosis and INRs,discusses the mechanistic pathways through which microbiota imbalance contributes to INRs development,and highlights how TCM interventions regulate gut microbiota to promote immune recovery.By focusing on the gut microbiota as a therapeutic interface,this article provides novel insights into TCM-based strategies for improving outcomes in INRs and supports the development of innovative treatment approaches.
基金supported by grants from the National Natural Science Foundation of China(No.82372382,82002333,32371412,and 32071349)the Central Guidance on Local Science and Technology Development Fund of Zhejiang Province(No.2024ZY01033)+1 种基金the Zhejiang Provincial Natural Science Foundation of China(No.LY24C100001)the Key Research and Development Program of Zhejiang(No.2022C01076).
文摘Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and osteoclast activity.However,the majority of research to date has focused on the direct effects of peripheral nerves and their neurotransmitters on bone regeneration.Emerging studies have begun to reveal a more intricate role of nerves in regulating the immune microenvironment,which is crucial for bone regeneration.This review summarizes how nerves influence bone regeneration through modulation of the immune microenvironment.We first discuss the changes in peripheral nerves during the regenerative process.We then describe conduction and paracrine pathways through which nerves affect the osteogenic immune microenvironment,emphasizing nerves,neural factors,and their impacts.Our goal is to deepen the understanding of the nerve-immune axis in bone regeneration.A better grasp of how nerves influence the osteogenic immune microenvironment may lead to new strategies that integrate the nervous,immune,and skeletal systems to promote bone regeneration.
基金funded by Ausnutria-kabrita Research Fund(RS2022-14).
文摘Probiotics can regulate the body’s immune system through both non-specific and specific immunity,thereby regulating host health.In terms of non-specific immune regulation,probiotics can activate the intrinsic immune system,regulate the mucosal barrier function,and play an immune role by influencing the activity of intrinsic immune cells such as macrophages,dendritic cells and natural killer cells,as well as their differentiation and maturation;in terms of specific immune regulation,probiotics play a role in regulating the immunoglobulin level and the maturation of B cells.Probiotics can also regulate T-cell differentiation according to the condition of the body,thus regulating specific immunity.Many studies have focused on the role of probiotics in metabolism and nutrition,and the mechanisms involved in the immunomodulatory role of probiotics have only been partially described.This review summarises the role of common probiotics such as Lactobacillus plantarum and Lactobacillus rhamnosus in immunomodulation as well as their mechanisms,describing the currently known mechanisms of immunomodulation by probiotics in improving the host immune system.A deeper understanding of probiotics and their specific mechanisms of action will facilitate the use of probiotics for immunomodulation in clinical medicine,functional foods,and other areas.This will also contribute to the development and research of engineered probiotics,next-generation probiotics,and other new functional probiotics with immunomodulatory effects.
基金supported by the National Natural Science Foundation of China(Nos.82573045,82460602,82560459)the Hainan Provincial Graduate Student Innovative Research Project(No.Qhys2024-440).
文摘Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.
基金Natural Science Foundation of Beijing,No.7244428(to WZ)Peking University Medicine Sailing Program for Young Scholars’Scientific and Technological Innovation,No.BMU2023YFJHPY034(to WZ)+1 种基金the National Natural Science Foundation of China,Nos.81873784(to DF),82071426(to DF)Clinical Cohort Construction Program of Peking University Third Hospital,Nos.BYSYDL2019002(to DF)and BYSYZD2021004(to DF).
文摘Amyotrophic lateral sclerosis is characterized by the progressive loss of motor neurons.Early-stage axonal dysfunction,rather than central nervous system injury,plays a key role in the disease process.However,the molecular mechanisms underlying this dysfunction remain unclear.To investigate the relationship between peripheral immune dysregulation and axonal dysfunction in amyotrophic lateral sclerosis,we recruited 372 patients within the first 12 months of sporadic amyotrophic lateral sclerosis onset between January 2018 and May 2024.We collected peripheral immune markers at baseline,including total leukocytes,lymphocytes,monocytes,neutrophils,basophils,eosinophils,and platelets.We also calculated four derived ratios:neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,lymphocyte-to-monocyte ratio,and systemic immune inflammation index.Multivariate analysis,adjusted for confounding factors,revealed that higher counts of total leukocytes and neutrophils,as well as higher neutrophil-related ratios,including the neutrophil to lymphocyte ratio and the systemic immune inflammation index,were significantly correlated with higher compound muscle action potential scores.Stratified analyses revealed that these associations varied by age and sex.Furthermore,mediation analysis demonstrated that axonal dysfunction plays a significant role in the relationship between immune markers and disease progression.These findings emphasize the critical role that peripheral immune dysregulation plays in amyotrophic lateral sclerosis progression by mediating peripheral nerve injury,particularly in the early stages of the disease.This study highlights the importance of the peripheral nervous system in the early stages of amyotrophic lateral sclerosis and provides new insights into disease mechanisms and potential therapeutic targets.
基金funded by the National Natural Science Foundation of China(Grant Nos.82204517 to T.Z.and 82404756 to J.Z.)the Science and Technology Program in Medicine and Health of Zhejiang Province(Grant No.2023KY726 to T.Z.).
文摘Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.
文摘Objective:To analyze the efficacy of allergen subcutaneous injection immunotherapy in patients with allergic rhinitis.Methods:Fifty patients with allergic rhinitis admitted from May 2023 to May 2025 were selected as study subjects and randomly divided into a control group and an observation group,with 25 patients in each group.The control group was treated with budesonide nasal spray,while the observation group received allergen subcutaneous injection immunotherapy in addition to the control treatment.The treatment efficacy,adverse reactions,symptom improvement time,and immune indicators were compared between the two groups.Results:The observation group showed a higher disease treatment efficacy than the control group(p<0.05);the incidence of adverse reactions in the observation group was not statistically significant compared to the control group(p>0.05);the observation group had a shorter symptom improvement time for nasal obstruction,rhinorrhea,and sneezing than the control group(p<0.05);before treatment,there was no statistical significance in immune indicators between the two groups(p>0.05);after treatment,CD3+and CD4/CD8+in the observation group were higher than those in the control group(p<0.05).Conclusion:Allergen subcutaneous injection immunotherapy in patients with allergic rhinitis can improve disease treatment efficacy,alleviate clinical symptoms,and enhance immune function.This therapy is safe and has clinical application value.
基金supported by the Nature Science Foundation of Liaoning Province,Nos.2022-MS-211,2021-MS-064,and 2024-MS-048(all to YC).
文摘Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.
基金Supported by National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-B-022,and No.2022-PUMCH-D-002CAMS Innovation Fund for Medical Sciences,No.CIFMS 2021-1-I2M-003Undergraduate Innovation Program,No.2024dcxm025.
文摘Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.
基金supported by the National Natural Science Foundation of China,Nos.82171082(to ZX),32000727(to TZ),32370731(to YZ)Guangdong Basic and Applied Basic Research Foundation,No.2024A151501069(to ZX)+1 种基金Shenzhen Science and Technology Program,Nos.JCYJ20210324101603009(to ZX),GJHZ20220913142807015(to TZ),JCYJ20220531100204010(to TZ),JCYJ20230807091308018(to YZ)Shenzhen Medical Research Funds,No.A2303068(to TZ).
文摘The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer’s disease.Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system,though the mechanisms are unclear.Here,we found that gamma-type immunoglobulin,a product originating from peripheral blood B cells,localized in the brain parenchyma of multiple mouse models with amyloid pathology,and was enriched on microglia but not on other brain cell types.Further experiments showed that gamma-type immunoglobulin bound to microglial cell membranes and led to diverse transcriptomic changes,including upregulation of pathways related to phagocytosis and immunity.Functional assays demonstrated that gamma-type immunoglobulin enhanced microglial phagocytic capacity for amyloid-beta fibrils via its Fc fragment,but not Fab fragment,fragment.Our data indicate that microglia,when exposed to gamma-type immunoglobulin,exhibit an enhanced capacity for clearing amyloid-beta fibrils,potentially via the gamma-type immunoglobulin Fc fragment signaling pathway.This suggests that parenchymal gamma-type immunoglobulin should be further investigated to determine whether it may play a beneficial role against Alzheimer’s disease by enhancing microglial function.
基金funded by the Research,Development,and Innovation Authority(RDIA)—Kingdom of Saudi Arabia(Grant No.13292-psu-2023-PSNU-R-3-1-EF-).
文摘Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.
文摘Glioblastoma(GBM),the most aggressive and lethal primary brain tumor in adults,continues to resist conventional therapeutic approaches,withmedian survival remaining dismally low.Immune checkpoint inhibitors(ICIs),which have revolutionized the treatment of several solid tumors,have shown limited efficacy inGBMowing to the highly immunosuppressive and heterogeneousmicroenvironment of the tumor.The unique immune landscape of the central nervous system(CNS),characterized by low immunogenicity,restricted T-cell infiltration,and an abundance of regulatory and myeloid-derived suppressor cells,poses considerable barriers to effective immune reactivation.This review provides a comprehensive synthesis of the mechanistic barriers undermining ICI efficacy in GBM,including the blood-brain barrier,low tumor mutational burden,adaptive immune resistance,and iatrogenic immunosuppression.It also explores emerging predictive and prognostic biomarkers,such as programmed death-ligand 1(PD-L1)expression,immune gene signatures,tumor-infiltrating lymphocyte profiles,and circulating markers in cerebrospinal fluid and plasma,which hold promise for guiding patient selection and therapeutic monitoring.Importantly,recent breakthroughs in combinatorial immunotherapy strategies are highlighted,including the integration of ICIs with radiotherapy,anti-angiogenic agents,oncolytic viruses,personalized neoantigen vaccines,and tumor microenvironment reprogramming approaches.Innovative delivery platforms,such as nanoparticles,focused ultrasound,and convection-enhanced delivery,are also discussed for their potential to improve drug bioavailability and local immune activation in the CNS.This review hypothesizes that the therapeutic efficacy of ICIs in GBM can be considerably enhanced by disrupting immune exclusion and reversing immunosuppression through integrated,multimodal strategies guided by dynamic biomarker profiling and spatially resolved immunemapping.This hypothesisdriven approach aims to bridge translational gaps and inform next-generation clinical trial designs that may unlock the potential of immunotherapy for GBM.
文摘Liver diseases are of growing interest to clinicians and researchers due to their high prevalence,difficulty in early diagnosis,and limited treatment options.The liver is an important organ at the intersection of many metabolic and immune pathways.To this end,it contains a large number of immune cells of both the innate and adaptive immune system that perform multiple functions,detecting and destroying pathogens that enter the body through the intestine,as well as recognizing endogenous antigens.Immune cells in the liver have a complex regulation that can be impaired in various diseases such as metabolic dysfunctionassociated steatotic liver disease(MASLD),liver cancer,and biliary diseases.A growing body of evidence reinforces the realization that not only impaired metabolism but also many immune mechanisms underlie MASLD.The liver has complex bilateral immune and metabolic links with the gut microbiota,and disruptions of these links underlie the development and progression of both gastrointestinal and other organ diseases.In this regard,acting on immune mechanisms is a promising therapeutic target for liver diseases.
基金supported by the National Key Research and Development Program of China(No.2022YFE0102100)the National Natural Science Foundation of China(Nos.U22A20307 and 81930041)。
文摘Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified;some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration(FDA) for clinical treatment. However, limited responses and immune-related adverse events(ir AEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.
