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
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
Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neu...Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.展开更多
Immunotherapy offers the promise of a potential cure for cancer,yet achieving the desired therapeutic effect can be challenging due to the immunosuppressive tumor microenvironments(TMEs) present in some tumors.Therefo...Immunotherapy offers the promise of a potential cure for cancer,yet achieving the desired therapeutic effect can be challenging due to the immunosuppressive tumor microenvironments(TMEs) present in some tumors.Therefore,robust immune system activation is crucial to enhance the efficacy of cancer immunotherapy in clinical applications.Bacteria have shown the ability to target the hypoxic TMEs while activating both innate and adaptive immune responses.Engineered bacteria,modified through chemical or biological methods,can be endowed with specific physiological properties,such as diverse surface antigens,metabolites,and improved biocompatibility.These unique characteristics give engineered bacteria distinct advantages in stimulating anti-cancer immune responses.This review explores the potential regulatory mechanisms of engineered bacteria in modulating both innate and adaptive immunity while also forecasting the future development and challenges of using engineered bacteria in clinical cancer immunotherapy.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
CD8^(+)T cell exhaustion,a critical challenge in the immune response to cancer,is characterized by a profound decline in the functionality of effector CD8^(+)T cells.This state of exhaustion is accompanied by the upre...CD8^(+)T cell exhaustion,a critical challenge in the immune response to cancer,is characterized by a profound decline in the functionality of effector CD8^(+)T cells.This state of exhaustion is accompanied by the upregulation of various inhibitory receptors and significant shifts in both transcriptional and epigenetic profiles,thus ultimately leading to inadequate tumor control.Therapeutic strategies aimed at reversing CD8^(+)T cell exhaustion have the potential to rejuvenate immune responses and enhance treatment efficacy.This review compiles current knowledge regarding the molecular mechanisms underlying CD8^(+)T cell exhaustion,including the roles of immune checkpoint molecules,the tumor microenvironment,metabolic reprogramming,transcription factors,and epigenetic modifications.Emerging therapeutic approaches designed to combat CD8^(+)T cell exhaustion are evaluated,with emphasis on the modulation of immune checkpoints;targeting of metabolic and transcriptional changes;and exploration of other innovative strategies,such as epigenetic editing and engineered CAR-T cells.Importantly,we expand the exhaustion concept to immune cells beyond CD8^(+)T cells,such as CD4^(+)T cells,natural killer cells,and myeloid populations,thereby highlighting the broader implications of systemic immunosuppression in the cancer context.Finally,we propose avenues for future research aimed at further elucidating the factors and molecular mechanisms associated with CD8^(+)T cell exhaustion,thereby underscoring the critical need for strategies aimed at reversing this state to improve outcomes in cancer immunotherapy.展开更多
Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underp...Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.展开更多
Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tum...Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tumor effects,they can also trigger immune-related adverse events(irAEs),with ICI-associated colitis being one of the more prevalent forms.This condition can disrupt treatment,necessitate drug discontinuation,and adversely affect therapeutic outcomes.In severe cases,irAEs may even become life-threatening.A recent case report by Hong et al highlights the importance of vigilance for ICI-associated colitis in patients experiencing symptoms such as diarrhea and abdominal pain,which can arise both during and even after completion of ICI treatment.Early identification,multidisciplinary management,and continuous monitoring of patients are essential steps to further improve outcomes.展开更多
Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary d...Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary disease(COPD).Disruptions in microbial balance during RV infections can impair immune homeostasis and worsen disease outcomes.Recent studies emphasize RV-induced regulation of antiviral defenses,cytokine production,and immune tolerance.This review explores the interplay between RV,the immune system,and microbiota,highlighting the importance of these interactions in guiding effective therapies for respiratory in-fections.It advances existing literature by considering microbiota-mediated therapies as a novel approach to managing RV exacerbations in respiratory diseases like asthma and COPD.展开更多
In 1891,a New York surgeon named William Coley injected cancer patients with live bacteria,observing with fascination as some tumors shrank amid raging fevers.His crude experiments-later deemed reckless-nonetheless re...In 1891,a New York surgeon named William Coley injected cancer patients with live bacteria,observing with fascination as some tumors shrank amid raging fevers.His crude experiments-later deemed reckless-nonetheless revealed a tantalizing truth:The immune system,when properly provoked,could attack cancer.Over a century later,researchers have transformed this observation into a precision strike force.展开更多
Glioblastoma(GBM)is one of the most aggressive and treatment-resistant brain cancers.Despite years of research and clinical trials,especially using immune checkpoint inhibitors,therapeutic gains remain minimal[1,2].A ...Glioblastoma(GBM)is one of the most aggressive and treatment-resistant brain cancers.Despite years of research and clinical trials,especially using immune checkpoint inhibitors,therapeutic gains remain minimal[1,2].A recent study published in Nature by Faust Akl and colleagues begins to lift the veil on this mystery,uncovering a previously unknown mechanism of immune evasion in GBM[3].展开更多
Sepsis is characterized by immune dysregulation that are responsible for an increase in secondary in-fections and mortality.Acupuncture is a potential alternative treatment for sepsis.In this comprehensive literature ...Sepsis is characterized by immune dysregulation that are responsible for an increase in secondary in-fections and mortality.Acupuncture is a potential alternative treatment for sepsis.In this comprehensive literature review,we found that acupuncture is beneficial in treating immune disorders associated with sepsis.Acupuncture can improve immune disorders associated with sepsis and regulate the functions of innate and adaptive immune cells.Specifically,acupuncture can reduce the number of neutrophils in sep-sis,promote the polarization of macrophages towards M2-like macrophages,and alleviate inflammation by reducing the activation of microglia and astrocytes.Furthermore,acupuncture can increase the per-centage of T cells and modulate the balance between T cell subsets.The immunomodulatory mechanism of acupuncture in sepsis may be attributed to the balance of the autonomic nervous system,including activation of the sympathetic-adrenal axis,vagal-cholinergic pathway,and vagal-adrenal axis.In addition,acupuncture can inhibit inflammation by preserving the integrity of the intestinal barrier and regulating the composition of the intestinal microbiota.Clinical studies have also demonstrated that acupuncture can enhance the number of peripheral natural killer(NK)cells and T cell subsets,as well as the expres-sion of human leukocyte antigen DR(HLA-DR).Moreover,acupuncture can decrease the ratio of white blood cells to neutrophils and reduce the levels of inflammatory factors.Therefore,acupuncture has the potential to improve immune function in sepsis.Further investigation of its mechanism is expected to provide a scientific and reliable foundation for the application of acupuncture in sepsis treatment.展开更多
To the editor:The liver’s immune-privileged status allows for a unique microenvironment that supports tumour growth and metastasis.In hepatocellular carcinoma(HCC),the balance between cytotoxic T lymphocytes and regu...To the editor:The liver’s immune-privileged status allows for a unique microenvironment that supports tumour growth and metastasis.In hepatocellular carcinoma(HCC),the balance between cytotoxic T lymphocytes and regulatory T cells plays a crucial role in determining patient outcomes.The expression of programmed cell death ligand 1(PD-1)and other immune checkpoint molecules contributes to a pro-tumourigenic microenvironment and is associated with poor prognosis.Additionally,the heterogeneity of the immune microenvironment adds complexity to disease progression and treatment response.展开更多
BACKGROUND Immunoglobulin G4(IgG4)-related disease(IgG4-RD),a relatively rare immunemediated chronic inflammatory condition characterized by fibrosis,is capable of affecting multiple organs and systems.Epidemiological...BACKGROUND Immunoglobulin G4(IgG4)-related disease(IgG4-RD),a relatively rare immunemediated chronic inflammatory condition characterized by fibrosis,is capable of affecting multiple organs and systems.Epidemiologically,the disease predominantly affects middle-aged and older men in Asian populations,whereas it shows a female predominance in the corresponding age group in the United States.In IgG4-RD,affected tissues and organs may exhibit diffuse or localized swelling,mimicking neoplastic lesions.IgG4-related cholecystitis(IgG4-CC)represents a manifestation involving the gallbladder,with isolated gallbladder involvement without other organ lesions being exceptionally uncommon.CASE SUMMARY A 53-year-old man was admitted to the hospital with abdominal pain.Preoperative evaluations could not exclude gallbladder carcinoma,and surgical intervention was required.Based on intraoperative findings,postoperative pathology,and postoperative serum IgG4 levels,a diagnosis of IgG4-CC was considered.After glucocorticoid therapy,the patient’s general condition substantially improved.CONCLUSION For patients present with space-occupying lesions of the gallbladder,IgG4-RD should be included in the differential diagnosis.展开更多
Lung cancer is a common cause of cancer-related death globally.The majority of lung cancer patients initially benefit from chemotherapy and immunotherapy.However,as the treatment cycle progresses and the disease evolv...Lung cancer is a common cause of cancer-related death globally.The majority of lung cancer patients initially benefit from chemotherapy and immunotherapy.However,as the treatment cycle progresses and the disease evolves,the emergence of acquired resistance leads to treatment failure.Many researches have shown that non-coding RNAs(ncRNAs)not only influence lung cancer progression but also act as potential mediators of immunotherapy and chemotherapy resistance in lung cancer,mediating drug resistance by regulating multiple targets and pathways.In addition,the regulation of immune response by ncRNAs is dualistic,forming a microenvironment for inhibits/promotes immune escape through changes in the expression of immune checkpoints.The aim of this review is to understand the effects of ncRNAs on the occurrence and development of lung cancer,focusing on the role of ncRNAs in regulating drug resistance of lung cancer.展开更多
The immune system is the body's main cancer surveillance system.Unlike surgery,radiation,and chemotherapy,which are typically nonspecific,cancer immunotherapy holds tremendous promise as it harnesses the high spec...The immune system is the body's main cancer surveillance system.Unlike surgery,radiation,and chemotherapy,which are typically nonspecific,cancer immunotherapy holds tremendous promise as it harnesses the high specificity of a person's immune system to kill cancer cells selectively.This promising approach includes checkpoint inhibitors,chimeric antigen receptor (CAR)-T cell therapy,cancer vaccines,cytokines,and monoclonal antibodies,among others.Cancer immunotherapy has progressed tremendously,resulting from basic science discoveries in the molecular and cellular biology of T cells.展开更多
Hepatocellular carcinoma(HCC)is a primary malignant tumor of the liver and one of the most common malignant tumors,as well as the third leading cause of cancer-related death.In recent years,immune checkpoint inhibitor...Hepatocellular carcinoma(HCC)is a primary malignant tumor of the liver and one of the most common malignant tumors,as well as the third leading cause of cancer-related death.In recent years,immune checkpoint inhibitors have emerged as a key strategy in cancer treatment.However,anti-programmed cell death 1/programmed death ligand 1 therapies,one of the main immunotherapeutic approaches,only elicit a response in only approximately 20%of advanced HCC.This suggests that there may be other immune checkpoints playing important roles in HCC immunotherapy.Recent studies have highlighted Signal regulatory protein alpha(SIRPα)is a phagocytic checkpoint in macrophages and other immune cells,as a promising novel therapeutic target in tumor immunotherapy.This review summarizes current progress on SIRPαin HCC and identifies key challenges for future related research.展开更多
Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host’s immune system,enhancing protection against subsequent infections.The concept ...Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host’s immune system,enhancing protection against subsequent infections.The concept of trained immunity has a significant impact on the field of immunology and has the potential to revolutionize how we approach vaccination and infectious disease control.Investigations into trained immunity are rapidly advanc-ing and have led to the development of new vaccines and immunotherapeutic strategies that harness the power of this phenomenon.While more investigations are needed to fully understand the mechanisms of trained immunity and its potential limitations,the prospects for its future application in clinical practice are promising.Here,we describe trained immunity as a biological process and explore the innate cues,epigenetic changes,and metabolic reprogram-ming activities that affect how trained immunity is induced.展开更多
High expression of pescadillo ribosomal biogenesis factor 1(PES1)has been re-ported across multiple cancer types and is significantly associated with poor prog-nosis.Hu et al in their recent paper described their inve...High expression of pescadillo ribosomal biogenesis factor 1(PES1)has been re-ported across multiple cancer types and is significantly associated with poor prog-nosis.Hu et al in their recent paper described their investigation of PES1 in gastric cancer and head and neck squamous cell carcinoma,demonstrating positive cor-relations between PES1 and programmed death-ligand 1(PD-L1)expression(51.72%for PES1 and 58.62%for PD-L1),as well as associations with lymph node metastasis and tumor invasion depth.However,the relationship between PES1 and PD-L1 remains incompletely defined.To further address this gap,we ana-lyzed The Cancer Genome Atlas gastric adenocarcinoma dataset and found a negative correlation between PES1 expression and CD8+T cell infiltration,along-side a positive correlation with PD-L1 expression.Based on prior findings,we hypothesize that PES1 may regulate PD-L1 through the phosphatidylinositol 3-kinase/protein kinase B pathway or cellular Myc-mediated mechanisms.While these pathways require experimental validation,our observations highlight PES1 as a potential regulator of immune evasion and a promising target for cancer immunotherapy.展开更多
BACKGROUND Radiotherapy(RT)is a cornerstone of cancer treatment.Compared with conven-tional high-dose radiation,low-dose radiation(LDR)causes less damage to normal tissues while potentially modulating immune responses...BACKGROUND Radiotherapy(RT)is a cornerstone of cancer treatment.Compared with conven-tional high-dose radiation,low-dose radiation(LDR)causes less damage to normal tissues while potentially modulating immune responses and inhibiting tumor growth.LDR stimulates both innate and adaptive immunity,enhancing the activity of natural killer cells,dendritic cells,and T cells.However,the me-chanisms underlying the effects of LDR on the immune system remain unclear.AIM To explore the history,research hotspots,and emerging trends in immune response to LDR literature over the past two decades.METHODS Publications on immune responses to LDR were retrieved from the Web of Science Core Collection.Bibliometric tools,including CiteSpace and HistCite,were used to identify historical features,active topics,and emerging trends in this field.RESULTS Analysis of 1244 publications over the past two decades revealed a significant surge in research on immune responses to LDR,particularly in the last decade.Key journals such as INR J Radiat Biol,Cancers,and Radiat Res published pivotal studies.Citation networks identified key studies by authors like Twyman-Saint Victor C(2015)and Vanpouille-Box C(2017).Keyword analysis revealed hotspots such as ipilimumab,stereotactic body RT,and targeted therapy,possibly identifying future research directions.Temporal variations in keyword clusters and alluvial flow maps illustrate the evolution of research themes over time.CONCLUSION This bibliometric analysis provides valuable insights into the evolution of studies on responses to LDR,highlights research trends,and identifies emerging areas for further investigation.展开更多
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.
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Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),project numbers 324633948 and 409784463(DFG grants Hi 678/9-3 and Hi 678/10-2,FOR2953)to HHBundesministerium für Bildung und Forschung-BMBF,project number 16LW0463K to HT.
文摘Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.
基金supported by the Science and Technology Research Project of Jilin Education Bureau(No.JJKH20230804KJ)。
文摘Immunotherapy offers the promise of a potential cure for cancer,yet achieving the desired therapeutic effect can be challenging due to the immunosuppressive tumor microenvironments(TMEs) present in some tumors.Therefore,robust immune system activation is crucial to enhance the efficacy of cancer immunotherapy in clinical applications.Bacteria have shown the ability to target the hypoxic TMEs while activating both innate and adaptive immune responses.Engineered bacteria,modified through chemical or biological methods,can be endowed with specific physiological properties,such as diverse surface antigens,metabolites,and improved biocompatibility.These unique characteristics give engineered bacteria distinct advantages in stimulating anti-cancer immune responses.This review explores the potential regulatory mechanisms of engineered bacteria in modulating both innate and adaptive immunity while also forecasting the future development and challenges of using engineered bacteria in clinical cancer immunotherapy.
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.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82171810)the Program of Shandong Provincial Scientific and Technological Development of Traditional Chinese Medicine(Grant No.M-2023210)。
文摘CD8^(+)T cell exhaustion,a critical challenge in the immune response to cancer,is characterized by a profound decline in the functionality of effector CD8^(+)T cells.This state of exhaustion is accompanied by the upregulation of various inhibitory receptors and significant shifts in both transcriptional and epigenetic profiles,thus ultimately leading to inadequate tumor control.Therapeutic strategies aimed at reversing CD8^(+)T cell exhaustion have the potential to rejuvenate immune responses and enhance treatment efficacy.This review compiles current knowledge regarding the molecular mechanisms underlying CD8^(+)T cell exhaustion,including the roles of immune checkpoint molecules,the tumor microenvironment,metabolic reprogramming,transcription factors,and epigenetic modifications.Emerging therapeutic approaches designed to combat CD8^(+)T cell exhaustion are evaluated,with emphasis on the modulation of immune checkpoints;targeting of metabolic and transcriptional changes;and exploration of other innovative strategies,such as epigenetic editing and engineered CAR-T cells.Importantly,we expand the exhaustion concept to immune cells beyond CD8^(+)T cells,such as CD4^(+)T cells,natural killer cells,and myeloid populations,thereby highlighting the broader implications of systemic immunosuppression in the cancer context.Finally,we propose avenues for future research aimed at further elucidating the factors and molecular mechanisms associated with CD8^(+)T cell exhaustion,thereby underscoring the critical need for strategies aimed at reversing this state to improve outcomes in cancer immunotherapy.
文摘Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.
基金Supported by 2021 Key Topic of Qinghai Provincial Health System–Guiding Plan Topic,No.2021-WJZDX-43.
文摘Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tumor effects,they can also trigger immune-related adverse events(irAEs),with ICI-associated colitis being one of the more prevalent forms.This condition can disrupt treatment,necessitate drug discontinuation,and adversely affect therapeutic outcomes.In severe cases,irAEs may even become life-threatening.A recent case report by Hong et al highlights the importance of vigilance for ICI-associated colitis in patients experiencing symptoms such as diarrhea and abdominal pain,which can arise both during and even after completion of ICI treatment.Early identification,multidisciplinary management,and continuous monitoring of patients are essential steps to further improve outcomes.
文摘Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary disease(COPD).Disruptions in microbial balance during RV infections can impair immune homeostasis and worsen disease outcomes.Recent studies emphasize RV-induced regulation of antiviral defenses,cytokine production,and immune tolerance.This review explores the interplay between RV,the immune system,and microbiota,highlighting the importance of these interactions in guiding effective therapies for respiratory in-fections.It advances existing literature by considering microbiota-mediated therapies as a novel approach to managing RV exacerbations in respiratory diseases like asthma and COPD.
文摘In 1891,a New York surgeon named William Coley injected cancer patients with live bacteria,observing with fascination as some tumors shrank amid raging fevers.His crude experiments-later deemed reckless-nonetheless revealed a tantalizing truth:The immune system,when properly provoked,could attack cancer.Over a century later,researchers have transformed this observation into a precision strike force.
文摘Glioblastoma(GBM)is one of the most aggressive and treatment-resistant brain cancers.Despite years of research and clinical trials,especially using immune checkpoint inhibitors,therapeutic gains remain minimal[1,2].A recent study published in Nature by Faust Akl and colleagues begins to lift the veil on this mystery,uncovering a previously unknown mechanism of immune evasion in GBM[3].
基金Supported by the National Natural Science Foundation of China:No.82374563,82004467,82305370China Postdoctoral Science Foundation:No.2022M721536+1 种基金Tianjin Graduate Research Innovation Project:2022BKY177TUTCM Graduate Research Innovation Project:YJSKC-20221016。
文摘Sepsis is characterized by immune dysregulation that are responsible for an increase in secondary in-fections and mortality.Acupuncture is a potential alternative treatment for sepsis.In this comprehensive literature review,we found that acupuncture is beneficial in treating immune disorders associated with sepsis.Acupuncture can improve immune disorders associated with sepsis and regulate the functions of innate and adaptive immune cells.Specifically,acupuncture can reduce the number of neutrophils in sep-sis,promote the polarization of macrophages towards M2-like macrophages,and alleviate inflammation by reducing the activation of microglia and astrocytes.Furthermore,acupuncture can increase the per-centage of T cells and modulate the balance between T cell subsets.The immunomodulatory mechanism of acupuncture in sepsis may be attributed to the balance of the autonomic nervous system,including activation of the sympathetic-adrenal axis,vagal-cholinergic pathway,and vagal-adrenal axis.In addition,acupuncture can inhibit inflammation by preserving the integrity of the intestinal barrier and regulating the composition of the intestinal microbiota.Clinical studies have also demonstrated that acupuncture can enhance the number of peripheral natural killer(NK)cells and T cell subsets,as well as the expres-sion of human leukocyte antigen DR(HLA-DR).Moreover,acupuncture can decrease the ratio of white blood cells to neutrophils and reduce the levels of inflammatory factors.Therefore,acupuncture has the potential to improve immune function in sepsis.Further investigation of its mechanism is expected to provide a scientific and reliable foundation for the application of acupuncture in sepsis treatment.
基金supported by Jiangsu Commission of Health(No.x202308)The Suzhou Gusu Health Talents Scientific Research Project(No.GSWS2021052).
文摘To the editor:The liver’s immune-privileged status allows for a unique microenvironment that supports tumour growth and metastasis.In hepatocellular carcinoma(HCC),the balance between cytotoxic T lymphocytes and regulatory T cells plays a crucial role in determining patient outcomes.The expression of programmed cell death ligand 1(PD-1)and other immune checkpoint molecules contributes to a pro-tumourigenic microenvironment and is associated with poor prognosis.Additionally,the heterogeneity of the immune microenvironment adds complexity to disease progression and treatment response.
基金Supported by the National Natural Science Foundation of Shandong Province,No.ZR2019QH008.
文摘BACKGROUND Immunoglobulin G4(IgG4)-related disease(IgG4-RD),a relatively rare immunemediated chronic inflammatory condition characterized by fibrosis,is capable of affecting multiple organs and systems.Epidemiologically,the disease predominantly affects middle-aged and older men in Asian populations,whereas it shows a female predominance in the corresponding age group in the United States.In IgG4-RD,affected tissues and organs may exhibit diffuse or localized swelling,mimicking neoplastic lesions.IgG4-related cholecystitis(IgG4-CC)represents a manifestation involving the gallbladder,with isolated gallbladder involvement without other organ lesions being exceptionally uncommon.CASE SUMMARY A 53-year-old man was admitted to the hospital with abdominal pain.Preoperative evaluations could not exclude gallbladder carcinoma,and surgical intervention was required.Based on intraoperative findings,postoperative pathology,and postoperative serum IgG4 levels,a diagnosis of IgG4-CC was considered.After glucocorticoid therapy,the patient’s general condition substantially improved.CONCLUSION For patients present with space-occupying lesions of the gallbladder,IgG4-RD should be included in the differential diagnosis.
文摘Lung cancer is a common cause of cancer-related death globally.The majority of lung cancer patients initially benefit from chemotherapy and immunotherapy.However,as the treatment cycle progresses and the disease evolves,the emergence of acquired resistance leads to treatment failure.Many researches have shown that non-coding RNAs(ncRNAs)not only influence lung cancer progression but also act as potential mediators of immunotherapy and chemotherapy resistance in lung cancer,mediating drug resistance by regulating multiple targets and pathways.In addition,the regulation of immune response by ncRNAs is dualistic,forming a microenvironment for inhibits/promotes immune escape through changes in the expression of immune checkpoints.The aim of this review is to understand the effects of ncRNAs on the occurrence and development of lung cancer,focusing on the role of ncRNAs in regulating drug resistance of lung cancer.
文摘The immune system is the body's main cancer surveillance system.Unlike surgery,radiation,and chemotherapy,which are typically nonspecific,cancer immunotherapy holds tremendous promise as it harnesses the high specificity of a person's immune system to kill cancer cells selectively.This promising approach includes checkpoint inhibitors,chimeric antigen receptor (CAR)-T cell therapy,cancer vaccines,cytokines,and monoclonal antibodies,among others.Cancer immunotherapy has progressed tremendously,resulting from basic science discoveries in the molecular and cellular biology of T cells.
基金Supported by the National Key Sci-Tech Special Project of China,No.2018ZX10302207the Beijing Natural Science Foundation,No.7222191+3 种基金the Beijing Natural Science Foundation,No.7244426the Fundamental Research Funds for the Central Universities,Peking University,No.PKU2024XGK005the Peking University Medicine Seed Fund for Interdisciplinary Research,No.BMU2021MX007 and No.BMU2022MX001Fundamental Research Funds for the Central Universities,Peking University People’s Hospital Scientific Research Development Funds,No.RDY2020-06 and No.RDJ2022-14.
文摘Hepatocellular carcinoma(HCC)is a primary malignant tumor of the liver and one of the most common malignant tumors,as well as the third leading cause of cancer-related death.In recent years,immune checkpoint inhibitors have emerged as a key strategy in cancer treatment.However,anti-programmed cell death 1/programmed death ligand 1 therapies,one of the main immunotherapeutic approaches,only elicit a response in only approximately 20%of advanced HCC.This suggests that there may be other immune checkpoints playing important roles in HCC immunotherapy.Recent studies have highlighted Signal regulatory protein alpha(SIRPα)is a phagocytic checkpoint in macrophages and other immune cells,as a promising novel therapeutic target in tumor immunotherapy.This review summarizes current progress on SIRPαin HCC and identifies key challenges for future related research.
文摘Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host’s immune system,enhancing protection against subsequent infections.The concept of trained immunity has a significant impact on the field of immunology and has the potential to revolutionize how we approach vaccination and infectious disease control.Investigations into trained immunity are rapidly advanc-ing and have led to the development of new vaccines and immunotherapeutic strategies that harness the power of this phenomenon.While more investigations are needed to fully understand the mechanisms of trained immunity and its potential limitations,the prospects for its future application in clinical practice are promising.Here,we describe trained immunity as a biological process and explore the innate cues,epigenetic changes,and metabolic reprogram-ming activities that affect how trained immunity is induced.
文摘High expression of pescadillo ribosomal biogenesis factor 1(PES1)has been re-ported across multiple cancer types and is significantly associated with poor prog-nosis.Hu et al in their recent paper described their investigation of PES1 in gastric cancer and head and neck squamous cell carcinoma,demonstrating positive cor-relations between PES1 and programmed death-ligand 1(PD-L1)expression(51.72%for PES1 and 58.62%for PD-L1),as well as associations with lymph node metastasis and tumor invasion depth.However,the relationship between PES1 and PD-L1 remains incompletely defined.To further address this gap,we ana-lyzed The Cancer Genome Atlas gastric adenocarcinoma dataset and found a negative correlation between PES1 expression and CD8+T cell infiltration,along-side a positive correlation with PD-L1 expression.Based on prior findings,we hypothesize that PES1 may regulate PD-L1 through the phosphatidylinositol 3-kinase/protein kinase B pathway or cellular Myc-mediated mechanisms.While these pathways require experimental validation,our observations highlight PES1 as a potential regulator of immune evasion and a promising target for cancer immunotherapy.
文摘BACKGROUND Radiotherapy(RT)is a cornerstone of cancer treatment.Compared with conven-tional high-dose radiation,low-dose radiation(LDR)causes less damage to normal tissues while potentially modulating immune responses and inhibiting tumor growth.LDR stimulates both innate and adaptive immunity,enhancing the activity of natural killer cells,dendritic cells,and T cells.However,the me-chanisms underlying the effects of LDR on the immune system remain unclear.AIM To explore the history,research hotspots,and emerging trends in immune response to LDR literature over the past two decades.METHODS Publications on immune responses to LDR were retrieved from the Web of Science Core Collection.Bibliometric tools,including CiteSpace and HistCite,were used to identify historical features,active topics,and emerging trends in this field.RESULTS Analysis of 1244 publications over the past two decades revealed a significant surge in research on immune responses to LDR,particularly in the last decade.Key journals such as INR J Radiat Biol,Cancers,and Radiat Res published pivotal studies.Citation networks identified key studies by authors like Twyman-Saint Victor C(2015)and Vanpouille-Box C(2017).Keyword analysis revealed hotspots such as ipilimumab,stereotactic body RT,and targeted therapy,possibly identifying future research directions.Temporal variations in keyword clusters and alluvial flow maps illustrate the evolution of research themes over time.CONCLUSION This bibliometric analysis provides valuable insights into the evolution of studies on responses to LDR,highlights research trends,and identifies emerging areas for further investigation.
