Cellular &Molecular Immunology最新文献_第2页

Regulatory heme: a mitochondria-to-nucleus messenger of CD8⁺ T-cell exhaustion. 调节性血红素：CD8+ t细胞耗竭的线粒体到细胞核信使。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2026-04-22 DOI: 10.1038/s41423-026-01420-z

Hao Song, Hao Shi, Hongbo Chi

引用次数: 0

Construction of an engineered Escherichia coli strain with enhanced intestinal colonization and anti-inflammatory efficacy in colitis. 具有增强结肠炎肠道定植和抗炎功效的工程大肠杆菌菌株的构建。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2026-04-22 DOI: 10.1038/s41423-026-01415-w

Peijun Yu, Wenjing Zhou, Chunyang Li, Qiang Sun, Yunpeng Yang

{"title":"Construction of an engineered Escherichia coli strain with enhanced intestinal colonization and anti-inflammatory efficacy in colitis.","authors":"Peijun Yu, Wenjing Zhou, Chunyang Li, Qiang Sun, Yunpeng Yang","doi":"10.1038/s41423-026-01415-w","DOIUrl":"https://doi.org/10.1038/s41423-026-01415-w","url":null,"abstract":"<p><p>Engineered probiotics are considered effective and safe therapeutic strategies for the treatment of various diseases. Escherichia coli Nissle 1917 (EcN) has been widely used as a chassis strain because of its safety and well-established genetic manipulation system. However, the limited intestinal colonization ability of EcN limits its potential as a chassis for the construction of synthetic probiotics. Here, an engineered EcN strain (EcN-CPM) with enhanced gastric acid and bile salt tolerance and improved intestinal adhesion was constructed. Oral administration of EcN-CPM to mice with colitis alleviated disease severity and reshaped the disordered gut microbiome by decreasing the abundance of Escherichia-Shigella while increasing the abundance of norank_f_Muribaculaceae. Mechanistically, the EcN-CPM supernatant directly promoted the proliferation of norank_f_Muribaculaceae, a short-chain fatty acid (SCFA)-producing genus. Targeted metabolomics revealed that EcN-CPM restored the DSS-induced depletion of SCFAs, which were negatively correlated with the abundance of Escherichia-Shigella and positively correlated with the abundance of norank_f_Muribaculaceae. Consistent with these findings, EcN-CPM treatment upregulated the expression of Treg-associated markers (Foxp3, Ctla4, and Cd25) and downregulated the expression of Th17-related genes (IL-17A and Roryt) in colonic tissues, restoring the IL-17A/Foxp3 ratio to homeostasis. Untargeted metabolomics further demonstrated that EcN-CPM uniquely restored the levels of seven anti-inflammatory metabolites depleted by DSS treatment. Collectively, these findings demonstrate that EcN-CPM alleviates intestinal inflammation by remodeling the gut microbiota to increase the production of SCFAs and anti-inflammatory metabolites, thereby driving a shift in Th17- and Treg-associated transcriptional signatures. This study establishes a platform for precision-designed synthetic probiotics with enhanced probiotic properties.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":19.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MAIT cell plasticity generates CD4+ MAIT cells that promote HCC progression via metabolic crosstalk with tumor cells MAIT细胞的可塑性产生CD4+ MAIT细胞，通过与肿瘤细胞的代谢串扰促进HCC的进展。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2026-04-14 DOI: 10.1038/s41423-026-01409-8

Sicheng Fu, Maoyu Tang, Changfeng Zhao, Sanwei Chen, Miya Su, Jun Pan, Yuwei Zhang, Xiaohu Wang, Wenhao Jia, Xinmin Chu, Shi Chen, Yusheng Chen, Lijian Chen, Tengchuan Jin, Zhigang Tian, Yubei Sun, Yeben Qian, Lianxin Liu, Hua Wang, Huimin Zhang, Li Bai

{"title":"MAIT cell plasticity generates CD4+ MAIT cells that promote HCC progression via metabolic crosstalk with tumor cells","authors":"Sicheng Fu, Maoyu Tang, Changfeng Zhao, Sanwei Chen, Miya Su, Jun Pan, Yuwei Zhang, Xiaohu Wang, Wenhao Jia, Xinmin Chu, Shi Chen, Yusheng Chen, Lijian Chen, Tengchuan Jin, Zhigang Tian, Yubei Sun, Yeben Qian, Lianxin Liu, Hua Wang, Huimin Zhang, Li Bai","doi":"10.1038/s41423-026-01409-8","DOIUrl":"10.1038/s41423-026-01409-8","url":null,"abstract":"Mucosal-associated invariant T cells (MAITs) are enriched in the liver and closely related to human hepatocellular carcinoma (HCC), but their role is controversial. Whether and how the plasticity of MAITs modulates HCC progression remain to be explored. Here, we revealed that CD4+ MAITs displaying Th17 features were the major source of IL-17A in human HCC. IL-17A from Th17-polarized CD4+ MAITs promoted HCC progression by enhancing lipid storage and tumor cell proliferation in a PPARα dependent manner. Additionally, we showed that both TCR-dependent and TCR-independent activation signaling induced Th17-polarized CD4+ MAIT differentiation and that strong signaling promoted their differentiation. Moreover, IL-17A production in CD4+ MAITs was promoted by glycolysis via posttranscriptional regulation, and tumor cell-derived kynurenine enhanced glycolysis and IL-17A production through the AHR pathway. These findings demonstrate that the plasticity of MAITs and the generation of CD4+ MAITs promote HCC progression via metabolic crosstalk with tumor cells.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 5","pages":"491-504"},"PeriodicalIF":19.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hepatocyte-derived LRG1 primes the liver for metastasis and impairs immunotherapy 肝细胞来源的LRG1启动肝脏转移并损害免疫治疗。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2026-04-10 DOI: 10.1038/s41423-026-01408-9

Guojie Long, Bing Cheng, Yue Jiang, Qiufeng Liu, Xiaoming Huang, Zhitong Niu, Qian Xiao, Xiangjun Qian, Chaoyin Wei, Jinxin Chen, Yingzhen Weng, Zheyu Zheng, Dandong Luo, Tao Ma, Ting Su, Qiongwei Tang, Panpan Wang, Yufeng Chen, Jing Tan, Ronghua Zhang, Qiang Yu, Weidong Pan, Wenyu Wang

{"title":"Hepatocyte-derived LRG1 primes the liver for metastasis and impairs immunotherapy","authors":"Guojie Long, Bing Cheng, Yue Jiang, Qiufeng Liu, Xiaoming Huang, Zhitong Niu, Qian Xiao, Xiangjun Qian, Chaoyin Wei, Jinxin Chen, Yingzhen Weng, Zheyu Zheng, Dandong Luo, Tao Ma, Ting Su, Qiongwei Tang, Panpan Wang, Yufeng Chen, Jing Tan, Ronghua Zhang, Qiang Yu, Weidong Pan, Wenyu Wang","doi":"10.1038/s41423-026-01408-9","DOIUrl":"10.1038/s41423-026-01408-9","url":null,"abstract":"The liver undergoes active remodeling by the primary tumor prior to metastatic spread. However, the mechanisms by which hepatocytes dictate the liver-specific tropism of tumors remain elusive. Here, we identify hepatocyte-derived leucine-rich alpha-2-glycoprotein 1 (LRG1) as a key mediator of liver premetastatic niche (PMN) formation. Clinically, elevated serum LRG1 levels are correlated with an increased risk of liver metastasis in patients and multiple mouse models. Mechanistically, LRG1 remodels the hepatic microenvironment by driving immunosuppressive neutrophil accumulation, impairing the function of effector T cells and dendritic cells, and enhancing angiogenesis in the liver, thereby fostering a prometastatic landscape. Hepatocyte-specific ablation of LRG1 dampens premetastatic niche formation and significantly reduces the metastatic burden in vivo. Hepatic LRG1 induced by tumor-associated inflammation via IL-6/STAT3 signaling promotes liver metastasis through the formation of TGFBR/PI3K/AKT axis-driven neutrophil extracellular traps (NETs). Importantly, therapeutic blockade of LRG1 not only suppressed liver metastasis but also reprogrammed the hepatic niche toward an immune-activated state, sensitizing tumors to anti-PD-1 therapy. Collectively, our findings reveal a hepatocyte–LRG1 axis that drives liver premetastatic niche remodeling and highlight LRG1 as a promising target for the prevention and treatment of liver metastasis.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 5","pages":"560-574"},"PeriodicalIF":19.8,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41423-026-01408-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653827","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

Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment 脂质代谢重编程塑造了肿瘤微环境中的免疫景观。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2026-04-07 DOI: 10.1038/s41423-026-01411-0

Yun-Wei Du, Ze-Rong Cai, Xiao-Tong Duan, Xin-Yu Li, Tong Yue, Tian Tian, Jian-Jun Li, Huai-Qiang Ju

{"title":"Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment","authors":"Yun-Wei Du, Ze-Rong Cai, Xiao-Tong Duan, Xin-Yu Li, Tong Yue, Tian Tian, Jian-Jun Li, Huai-Qiang Ju","doi":"10.1038/s41423-026-01411-0","DOIUrl":"10.1038/s41423-026-01411-0","url":null,"abstract":"Given the fundamental biological importance of lipids not only as structural components and energy substrates but also as potent bioactive molecules that govern immune and oncogenic signaling, lipid metabolism reprogramming has emerged as a central driver of tumor progression. Rather than merely fueling tumor growth, this extensive metabolic rewiring profoundly reshapes the tumor microenvironment (TME), establishing complex metabolic crosstalk that actively drives immune evasion. This review examines the current understanding of lipid metabolism reprogramming across different cellular compartments within the TME and its far-reaching implications for cancer immunotherapy. We first delineate how altered lipid metabolism directly fuels tumor cell proliferation, survival, and metastatic potential. We then examine the distinct lipid metabolic patterns in different immune cells, detailing how this reprogramming drives dysfunction in antitumor subsets such as CD8+ T cells and natural killer cells and how it promotes immunosuppressive populations such as tumor-associated macrophages and myeloid-derived suppressor cells. In addition to these immune alterations, we address the metabolic rewiring of stromal cells, particularly cancer-associated fibroblasts. Furthermore, by exploring intricate intercellular crosstalk, we highlight how tumor lipid metabolism promotes immune escape and how lipids from reprogrammed immune and stromal cells, in turn, support tumor growth, thereby reinforcing an immunosuppressive niche. Finally, we highlight emerging therapeutic strategies targeting these pathways and discuss how leveraging multiomics advances can translate lipid insights into cancer immunotherapy.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 5","pages":"457-470"},"PeriodicalIF":19.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41423-026-01411-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632200","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

Persistent IFN-I signaling inhibits mitochondrial oxidative metabolism in CD8+ T cells during HIV-1 infection under cART 在cART下HIV-1感染期间，持续的IFN-I信号抑制CD8+ T细胞的线粒体氧化代谢。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2026-04-02 DOI: 10.1038/s41423-026-01398-8

Liang Cheng, Guangming Li, Fei Luo, Wenwen Bi, Mengmeng Lu, Na Liu, Qiuchen Zhao, Runpeng Han, Hongyu Wang, Hao Yang, Jianping Ma, Wenjia Hu, Haisheng Yu, Wei Hou, Yong Xiong, Nilu Goonetilleke, R. Brad Jones, Lishan Su

{"title":"Persistent IFN-I signaling inhibits mitochondrial oxidative metabolism in CD8+ T cells during HIV-1 infection under cART","authors":"Liang Cheng, Guangming Li, Fei Luo, Wenwen Bi, Mengmeng Lu, Na Liu, Qiuchen Zhao, Runpeng Han, Hongyu Wang, Hao Yang, Jianping Ma, Wenjia Hu, Haisheng Yu, Wei Hou, Yong Xiong, Nilu Goonetilleke, R. Brad Jones, Lishan Su","doi":"10.1038/s41423-026-01398-8","DOIUrl":"10.1038/s41423-026-01398-8","url":null,"abstract":"Persistent type I interferon (IFN-I) signaling contributes to immune exhaustion and promotes HIV-1 persistence. While we and others have demonstrated that blocking IFN-I signaling in vivo restores anti-HIV-1 T-cell function and reduces viral reservoirs, the underlying mechanism remains unclear. Here, we showed that in humanized mice (hu-mice) and cells from people living with HIV-1 (PLWH), IFN-I signaling impaired mitochondrial activity in CD8+ T cells during chronic HIV-1 infection with effective antiretroviral therapy. Reprogramming immunometabolism by transient inhibition of glycolysis with 2-deoxy-D-glucose (2-DG) rescued mitochondrial activity, reversed aberrant immune activation, and enhanced CD8+ T-cell activity in HIV-infected hosts, both ex vivo and in vivo. When combined with an HIV-1 reservoir-activating agent, 2-DG reduced the viral reservoir size in hu-mice and suppressed HIV-1 amplification in cells from PLWH. These findings indicate that 2-DG-mediated immunometabolic reprogramming represents a novel strategy to restore host immunity and control HIV-1 reservoirs.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 5","pages":"534-545"},"PeriodicalIF":19.8,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acute stress alleviates type 2 lung inflammation by restricting ILC2s through corticosterone-glucocorticoid receptor signaling 急性应激可通过皮质激素-糖皮质激素受体信号传导抑制ILC2s，从而缓解2型肺部炎症。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2026-04-02 DOI: 10.1038/s41423-026-01407-w

Lin Zhu, Yuying Huang, Bo Peng, Shufeng Zhong, Xiaoyu Zhang, Fuyang Xiao, Dilare Asim, Jieken Pakezhati, Jinquan Ma, Siying Sun, Jiefang Xu, Shipeng Cheng, Liyan Ma, Zhiyang Ling, Chuyan Yi, Dongmei Lu, Junqin Liang, Bing Sun

{"title":"Acute stress alleviates type 2 lung inflammation by restricting ILC2s through corticosterone-glucocorticoid receptor signaling","authors":"Lin Zhu, Yuying Huang, Bo Peng, Shufeng Zhong, Xiaoyu Zhang, Fuyang Xiao, Dilare Asim, Jieken Pakezhati, Jinquan Ma, Siying Sun, Jiefang Xu, Shipeng Cheng, Liyan Ma, Zhiyang Ling, Chuyan Yi, Dongmei Lu, Junqin Liang, Bing Sun","doi":"10.1038/s41423-026-01407-w","DOIUrl":"10.1038/s41423-026-01407-w","url":null,"abstract":"The psychological state profoundly influences immune responses. While chronic stress is generally known to exacerbate inflammation, the impact of acute stress on inflammation has received far less attention. Here, we report that acute stress suppressed group 2 innate lymphoid cell (ILC2) responses, thereby alleviating type 2 lung inflammation. Restraint stress-induced acute stress activated the hypothalamic–pituitary–adrenal (HPA) axis and subsequently increased corticosterone levels. Corticosterone protected mice against lung inflammation by limiting ILC2 proliferation and type 2 cytokine production via the glucocorticoid receptor (GR). Adrenalectomy and genetic perturbation of the GR in ILC2s abolished acute stress-mediated immunosuppressive effects. Mechanistic studies revealed that corticosterone-GR signaling impaired ILC2 responses to microenvironmental factors by dampening downstream NF-κB and JAK-STAT signaling. Collectively, these findings reveal that acute stress alleviates ILC2-mediated lung inflammation through the neuroendocrine circuit and demonstrate the inhibitory role of endogenous corticosterone in ILC2 responses.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 5","pages":"546-559"},"PeriodicalIF":19.8,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SPT6 maintains epidermal homeostasis by inhibiting an NF-κB-positive feedback loop to prevent excessive inflammation SPT6通过抑制NF-κ b阳性反馈回路来维持表皮稳态，以防止过度炎症。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2026-04-01 DOI: 10.1038/s41423-026-01410-1

Yushuang Sun, Shuqia Xu, Dongyu Wang, Shuiying Gao, Xiaowen Qi, Miao Jiang, Dan Jian, Yaqiong Li, Zhaoyan Jiang, Miao Zhen, Peng Wang, Bin Shu, Julin Xie, Demeng Chen, Qing Tang, Jingting Li

{"title":"SPT6 maintains epidermal homeostasis by inhibiting an NF-κB-positive feedback loop to prevent excessive inflammation","authors":"Yushuang Sun, Shuqia Xu, Dongyu Wang, Shuiying Gao, Xiaowen Qi, Miao Jiang, Dan Jian, Yaqiong Li, Zhaoyan Jiang, Miao Zhen, Peng Wang, Bin Shu, Julin Xie, Demeng Chen, Qing Tang, Jingting Li","doi":"10.1038/s41423-026-01410-1","DOIUrl":"10.1038/s41423-026-01410-1","url":null,"abstract":"Keratinocytes are increasingly recognized as central regulators of cutaneous immune responses and key contributors to maintaining immune homeostasis. However, whether and how epidermal stem and progenitor cells (EPSCs) actively suppress proinflammatory signaling pathways to prevent excessive inflammation and maintain epidermal immune quiescence remains unclear. Here, we generated a conditional knockout mouse model (K14-CreERT; Supt6fl/fl) to investigate the role of SPT6, a transcription elongation factor, in epidermal and immune homeostasis. Loss of SPT6 in basal keratinocytes led to spontaneous, psoriasis-like skin inflammation, characterized by epidermal hyperplasia, immune cell infiltration, parakeratosis, and hyperkeratosis. SPT6-deficient mice also exhibited significantly delayed wound healing accompanied by impaired Wnt signaling. Moreover, single-cell RNA sequencing revealed distinct keratinocyte subpopulations with inflammatory signatures, elevated NF-κB signaling, and suppressed Wnt signaling. Mechanistically, SPT6 suppresses NF-κB signaling by binding to an enhancer of the RELA gene and preventing its positive transcriptional feedback loop. These findings support a new paradigm in which the default state of the skin may be primed for inflammation, and active suppression by factors such as SPT6 is required to maintain epidermal homeostasis. Taken together, the results of our study reveal a previously unrecognized role for SPT6 as a key regulator of epidermal immune quiescence and tissue integrity.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 5","pages":"471-490"},"PeriodicalIF":19.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41423-026-01410-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589907","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

T cell adaptation in chronic infections and tumors 慢性感染和肿瘤中的T细胞适应。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2026-03-30 DOI: 10.1038/s41423-026-01405-y

Hendrik Luxenburger, Robert Thimme, Maike Hofmann

{"title":"T cell adaptation in chronic infections and tumors","authors":"Hendrik Luxenburger, Robert Thimme, Maike Hofmann","doi":"10.1038/s41423-026-01405-y","DOIUrl":"10.1038/s41423-026-01405-y","url":null,"abstract":"Chronic viral infections and cancer challenge immune control by enforcing sustained antigen exposure, which profoundly alters the fate and function of CD8+ T cells. In contrast to acute infections, which induce robust effector differentiation and durable immune memory, persistent infections and tumors drive CD8+ T cells into distinct states of functional adaptation. The best studied chronic adaptation is T cell exhaustion, which is characterized by impaired effector functions, reduced proliferative capacity, sustained expression of inhibitory receptors, and stable transcriptional and epigenetic reprogramming. T cell exhaustion is not a uniform or terminal condition but comprises heterogeneous and dynamic cellular states, including stem-like/precursor populations that retain self-renewal capacity and therapeutic responsiveness. These insights have reshaped our understanding of immune regulation in chronic disease and underpin the success of immune checkpoint blockade therapies. However, heterogeneous and often transient clinical responses highlight critical gaps in our mechanistic understanding of exhausted T cell biology. This review synthesizes recent advances in the cellular and molecular profiling of chronically stimulated CD8+ T cells across chronic viral infection and cancer, focusing on regulatory networks, defining factors, and tissue-specific cues that govern functional adaptation and exploring emerging therapeutic reprogramming strategies.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 5","pages":"440-456"},"PeriodicalIF":19.8,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41423-026-01405-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580699","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

Defining lytic IFNγ for deciphering the CTL mechanism 定义裂解IFNγ以破译CTL机制。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2026-03-25 DOI: 10.1038/s41423-026-01402-1

Jaewoo Park, SangJoon Lee

引用次数: 0