Cellular &Molecular Immunology最新文献_第3页

The gut microbiota in cancer immunity and immunotherapy 肠道微生物群在癌症免疫和免疫治疗中的作用。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-06 DOI: 10.1038/s41423-025-01326-2

Mingxu Xie, Xiang Li, Harry Cheuk-Hay Lau, Jun Yu

{"title":"The gut microbiota in cancer immunity and immunotherapy","authors":"Mingxu Xie, Xiang Li, Harry Cheuk-Hay Lau, Jun Yu","doi":"10.1038/s41423-025-01326-2","DOIUrl":"10.1038/s41423-025-01326-2","url":null,"abstract":"The human gastrointestinal tract harbors trillions of microorganisms, including bacteria, fungi, and viruses, to form the gut microbiota. Cumulative evidence has demonstrated the critical impact of gut microbes on cancer immunity. In cancer, an altered gut microbiota enriched with pathogenic bacteria can actively promote immune evasion and disrupt antitumor immunity, thereby supporting tumor growth and survival. Conversely, beneficial commensal bacteria (e.g., Lactobacillus and Bifidobacterium) have emerged as therapeutic probiotics for cancer prevention and as adjuvants for cancer therapy. The gut microbiota is also closely linked to the efficacy of immunotherapy. This review summarizes the effects of pathogenic bacteria and beneficial commensals, including T cells, B cells, natural killer cells, innate lymphoid cells, and myeloid-derived suppress cells, on various innate and adaptive immune cell populations in cancer. It also explores the mechanisms by which the gut microbiota influences immunotherapy efficacy, such as the modulation of innate immune cells and CD8+ T cells. Given its importance, an increasing number of studies have developed approaches to target the gut microbiota to improve immunotherapy outcomes and reduce immune-related adverse events. These strategies include antimicrobial intervention, probiotics, prebiotics/dietary modifications, microbial metabolites, phage therapy, and fecal microbiota transplantation. This review also evaluates clinical applications that use the gut microbiota to predict immunotherapy outcomes. Overall, the current understanding of host‒microbe interactions within the tumor microenvironment has laid a critical foundation for the translation of microbiota research into clinical practice, ultimately benefiting patients.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 9","pages":"1012-1031"},"PeriodicalIF":19.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Provocation and palliation—the dual roles of dermal white adipose tissue in neutrophilic skin inflammation 激发和缓解-真皮白色脂肪组织在中性粒细胞皮肤炎症中的双重作用。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-06 DOI: 10.1038/s41423-025-01332-4

Sahiti Marella, Allison C. Billi

引用次数: 0

Immunoglobulin divalence promotes B-cell antigen receptor cluster scale-dependent functions 免疫球蛋白二价促进b细胞抗原受体簇规模依赖性功能。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-06 DOI: 10.1038/s41423-025-01327-1

Erdem Yilmaz, Amirmohammad Rahimi, Matthias Münchhalfen, Mihai Alevra, Arash Golmohammadi, Christian Tetzlaff, Felipe Opazo, Niklas Engels

{"title":"Immunoglobulin divalence promotes B-cell antigen receptor cluster scale-dependent functions","authors":"Erdem Yilmaz, Amirmohammad Rahimi, Matthias Münchhalfen, Mihai Alevra, Arash Golmohammadi, Christian Tetzlaff, Felipe Opazo, Niklas Engels","doi":"10.1038/s41423-025-01327-1","DOIUrl":"10.1038/s41423-025-01327-1","url":null,"abstract":"Antibodies, also known as immunoglobulins, share an evolutionarily conserved dimeric core structure with two antigen binding sites. However, recognition of foreign molecules can be achieved by monovalent binding domains, as evidenced by the T-cell antigen receptor and various innate immune receptors. Thus, the reason for the strict evolutionary conservation of immunoglobulin divalence remains unclear. In addition to being soluble immune effector molecules, each immunoglobulin is also expressed as a membrane-bound isoform in the context of the B-cell antigen receptor (BCR). Here, we generated monovalent BCRs and found that their signaling and antigen internalization capabilities were strongly impaired. By using advanced superresolution imaging of BCRs following stimulation with antigens of distinct valences, we showed that the receptor cluster scale in the plasma membrane determines the magnitude of intracellular signaling. The incorporation of additional ITAMs into single BCRs did not increase receptor sensitivity but caused cellular desensitization. Our results demonstrate that the BCR-controlled signaling machinery senses the clustering status of the BCR and that subtle changes in cluster sizes are translated into cellular responses. These findings improve our knowledge of adaptive immune receptor function and will aid in the design of synthetic chimeric antigen receptors.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 9","pages":"1093-1108"},"PeriodicalIF":19.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PANoptosis in cancer: bridging molecular mechanisms to therapeutic innovations PANoptosis在癌症中的应用：连接分子机制与治疗创新。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-28 DOI: 10.1038/s41423-025-01329-z

Jin-Fei Lin, Ting-Ting Wang, Ren-Ze Huang, Yue-Tao Tan, Dong-Liang Chen, Huai-Qiang Ju

{"title":"PANoptosis in cancer: bridging molecular mechanisms to therapeutic innovations","authors":"Jin-Fei Lin, Ting-Ting Wang, Ren-Ze Huang, Yue-Tao Tan, Dong-Liang Chen, Huai-Qiang Ju","doi":"10.1038/s41423-025-01329-z","DOIUrl":"10.1038/s41423-025-01329-z","url":null,"abstract":"PANoptosis, a newly defined inflammatory programmed cell death, plays key roles in tumor development and progression. This process involves the assembly of PANoptosome complexes under various stimuli, which activate multiple cell death pathways simultaneously. By integrating key sensors and effector molecules, PANoptosis enhances immunogenic cell death while counteracts immune evasion mechanisms. This review focuses on current research of PANoptosis in cancer. Clinically, PANoptosis-related signatures show clinical value for predicting patient survival, discerning tumor immune microenvironment (TIME) characteristics and evaluating the therapeutic response. Mechanistically, complex signaling networks regulate PANoptosis, which in turn influences tumor behavior through dynamic interactions with TIME components. Therapeutically, targeting PANoptosis-related pathways, including nanomedicine approaches, demonstrate encouraging preclinical results. Particularly, combining PANoptosis modulation with radiotherapy, chemotherapy, or immunotherapy enhances anti-tumor efficacy. These findings position PANoptosis as a promising therapeutic target for reshaping TIME, overcoming treatment resistance, and improving cancer outcomes. Future research will focus on elucidating context-dependent PANoptosome regulation and translating these insights into precision oncology strategies.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 9","pages":"996-1011"},"PeriodicalIF":19.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myeloid cells in chronic liver inflammation 慢性肝脏炎症中的髓样细胞。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-28 DOI: 10.1038/s41423-025-01324-4

Dimitrios Patseas, Ahmed El-Masry, Zuobin Liu, Prakash Ramachandran, Evangelos Triantafyllou

引用次数: 0

Notch2−expressing CD4+ T cells attain immunoregulatory functions during autoimmune inflammation 表达notch2的CD4+ T细胞在自身免疫性炎症中获得免疫调节功能。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-23 DOI: 10.1038/s41423-025-01318-2

So-Eun Bae, Sang-Heon Park, Chae Youn Kim, Cho-Rong Lee, Chanyeon Lee, Rosah May Payumo, So Yeon Kim, Kyu-Young Sim, Ho Jin Kim, Hyungseok Seo, Seong-Joon Koh, Seunghee Hong, Sung-Gyoo Park

{"title":"Notch2−expressing CD4+ T cells attain immunoregulatory functions during autoimmune inflammation","authors":"So-Eun Bae, Sang-Heon Park, Chae Youn Kim, Cho-Rong Lee, Chanyeon Lee, Rosah May Payumo, So Yeon Kim, Kyu-Young Sim, Ho Jin Kim, Hyungseok Seo, Seong-Joon Koh, Seunghee Hong, Sung-Gyoo Park","doi":"10.1038/s41423-025-01318-2","DOIUrl":"10.1038/s41423-025-01318-2","url":null,"abstract":"Autoantigen−specific CD4+ T cells are central to the development of autoimmune diseases, while the expansion of regulatory T (Treg) cells expressing Forkhead box protein 3 (Foxp3) is essential for mitigating these conditions. In this study, we identified CD4+Notch2+Foxp3lo T cells in the spinal cords of mice with experimental autoimmune encephalomyelitis (EAE), dextran sodium sulfate−induced colitis model mice, and patients with ulcerative colitis as immune regulatory cells. These cells exhibited a nonproliferative, dysfunctional phenotype and demonstrated immune regulatory functions, including suppressive activity against activated CD4+ T cells and marked Treg cell expansion activity. Our data revealed that Notch2 deletion in Foxp3−expressing cells diminishes the ability of this population to reverse the clinical symptoms of EAE. Collectively, these findings suggest that Notch2 expression in dysfunctional CD4+ T cells plays a crucial role in immune regulation.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 9","pages":"1077-1092"},"PeriodicalIF":19.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of exosomes in immunopathology and potential therapeutic implications 外泌体在免疫病理中的作用及其潜在的治疗意义。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-14 DOI: 10.1038/s41423-025-01323-5

Wenhui Wang, Shuya Qiao, Xianghui Kong, Gensheng Zhang, Zhijian Cai

{"title":"The role of exosomes in immunopathology and potential therapeutic implications","authors":"Wenhui Wang, Shuya Qiao, Xianghui Kong, Gensheng Zhang, Zhijian Cai","doi":"10.1038/s41423-025-01323-5","DOIUrl":"10.1038/s41423-025-01323-5","url":null,"abstract":"Extracellular vesicles (EVs), including exosomes, ectosomes, and apoptotic bodies, are released by various cells. Among these subtypes, exosomes have been extensively studied and demonstrated to be crucial mediators of intercellular communication involving multiple physiological and pathological processes. Four primary steps influence the biogenesis of exosomes: generation of early endosomes, formation and maturation of multivesicular bodies (MVBs), MVB and plasma membrane fusion for exosome release, and MVB fusion with lysosomes for degradation. During the formation and maturation of MVBs, the main effector molecules, such as RNAs and proteins, are sorted into exosomes via diverse mechanisms. However, the effector molecules of exosomes are dynamic and reflect cell states in real time. Therefore, exosomes secreted by cells under disease conditions are often pathogenic. This review focuses on recent advances in the understanding of exosome biogenesis and the immunopathological effects of exosomes. In addition, potential strategies to mitigate the pathological effects of exosomes are summarized in this review.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 9","pages":"975-995"},"PeriodicalIF":19.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD8+GZMK+CD27+CCR7+ T cells mobilized by splenic sympathetic nerves aggravate brain ischemia‒reperfusion injury via CCL19-positive endothelial cells 脾交感神经动员CD8+GZMK+CD27+CCR7+ T细胞通过ccl19阳性内皮细胞加重脑缺血再灌注损伤。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-14 DOI: 10.1038/s41423-025-01311-9

Ying Bai, Hui Ren, Shuo Leng, Mengqin Yuan, YiXin Jiang, Shenyang Zhang, Yu Wang, Minzi Ju, Zhi Wang, Wen Xi, Lian Xu, Bingjing Zheng, Daxing Li, Xinchen Huo, Tianhao Zhu, Beicheng Zhang, Ling Shen, Yuan Zhang, Wei Jiang, John H. Zhang, Bing Han, Honghong Yao

{"title":"CD8+GZMK+CD27+CCR7+ T cells mobilized by splenic sympathetic nerves aggravate brain ischemia‒reperfusion injury via CCL19-positive endothelial cells","authors":"Ying Bai, Hui Ren, Shuo Leng, Mengqin Yuan, YiXin Jiang, Shenyang Zhang, Yu Wang, Minzi Ju, Zhi Wang, Wen Xi, Lian Xu, Bingjing Zheng, Daxing Li, Xinchen Huo, Tianhao Zhu, Beicheng Zhang, Ling Shen, Yuan Zhang, Wei Jiang, John H. Zhang, Bing Han, Honghong Yao","doi":"10.1038/s41423-025-01311-9","DOIUrl":"10.1038/s41423-025-01311-9","url":null,"abstract":"Splenic sympathetic activity critically modulates peripheral immunity after ischemic stroke, thus intervention in spleen sympathetic activity represents a promising therapeutic strategy for stroke. However, the mechanisms underlying spleen-brain-immune axis communication remain poorly understood. Here, we utilized a surgical denervation protocol to perform splenic sympathetic denervation (SDN), which significantly attenuated brain injury following stroke. Through single-cell RNA sequencing, we identified a novel GZMK+CD8+CD27+CCR7+ T-cell subset in patients with acute ischemic stroke (AIS), which we designated stroke-associated T (Tsa) cells. The expansion of Tsa cells was positively correlated with the severity of clinical symptoms and was driven by the splenic sympathetic nervous system. Stroke-induced sympathetic activation triggers the release of splenic norepinephrine (NE), which preferentially signals through ADRB2 on Tsa cells to promote their mobilization. Additionally, ischemic injury induces endothelial cell-specific expression of CCL19, which chemoattracts Tsa cells into the brain parenchyma via their cognate CCR7 receptor, exacerbating neuroinflammatory injury and neurological deficits in a transient middle cerebral artery occlusion (tMCAO) mouse model. We developed a CCR7-targeting peptide to disrupt this chemotactic axis and reduce T-cell infiltration, thereby mitigating brain injury. Our findings highlight SDN as a promising therapeutic strategy to attenuate ischemia‒reperfusion injury and suggest its potential as an adjunctive therapy for reperfusion treatment in AIS patients.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 9","pages":"1061-1076"},"PeriodicalIF":19.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL-17-secreting γδ T-cell-driven Siglec-F+ neutrophils mediate lung pathology in emphysema 分泌il -17的γδ t细胞驱动的Siglec-F+中性粒细胞介导肺气肿的肺病理。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-11 DOI: 10.1038/s41423-025-01322-6

Kingston H. G. Mills

引用次数: 0

Cholesterol promotes autoimmune pathology through T follicular helper cells 胆固醇通过T滤泡辅助细胞促进自身免疫病理。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-10 DOI: 10.1038/s41423-025-01319-1

Wei Li, George C. Tsokos

引用次数: 0