Immunity最新文献_第10页

T cells with a taste for tissue remodeling 有组织重塑嗜好的T细胞

IF 32.4 1区医学

Immunity Pub Date : 2025-04-08 DOI: 10.1016/j.immuni.2025.03.012

Greet Verstichel, Hilde Cheroutre

引用次数: 0

More than the sum: How vascular endothelial growth factor inhibition unlocks the full potential of immune checkpoint blockade 超过总和：血管内皮生长因子抑制如何解锁免疫检查点封锁的全部潜力

IF 32.4 1区医学

Immunity Pub Date : 2025-04-08 DOI: 10.1016/j.immuni.2025.03.009

Daniel H. Shu, Mark Yarchoan

引用次数: 0

2-5A is an immunotransmitter that fuels RNase L immunity 2-5A是一种促进RNase L免疫的免疫递质

IF 32.4 1区医学

Immunity Pub Date : 2025-04-08 DOI: 10.1016/j.immuni.2025.03.007

Songnan Wang, Lingyin Li

引用次数: 0

IL-9 and ZBTB18 are germinal center memory makers IL-9和ZBTB18是生发中心记忆制造者

IF 32.4 1区医学

Immunity Pub Date : 2025-04-08 DOI: 10.1016/j.immuni.2025.03.010

Erica L. Stewart, Deborah L. Burnett

引用次数: 0

Glia get RIPped in ALS 肌萎缩侧索硬化症患者神经胶质细胞被撕裂

IF 32.4 1区医学

Immunity Pub Date : 2025-04-08 DOI: 10.1016/j.immuni.2025.03.013

Alexis M. Johnson, John R. Lukens

引用次数: 0

Mitochondrial DNA released by senescent tumor cells enhances PMN-MDSC-driven immunosuppression through the cGAS-STING pathway 衰老肿瘤细胞释放的线粒体DNA通过cGAS-STING途径增强pmn - mdsc驱动的免疫抑制

IF 32.4 1区医学

Immunity Pub Date : 2025-04-08 DOI: 10.1016/j.immuni.2025.03.005

Ping Lai, Lei Liu, Nicolò Bancaro, Martina Troiani, Bianca Calì, Yuxin Li, Jingjing Chen, Prafull Kumar Singh, Rydell Alvarez Arzola, Giuseppe Attanasio, Nicolò Pernigoni, Emiliano Pasquini, Simone Mosole, Andrea Rinaldi, Jacopo Sgrignani, Shi Qiu, Pan Song, Yingrui Li, Maria Andrea Desbats, Azucena Rendón Ángel, Andrea Alimonti

{"title":"Mitochondrial DNA released by senescent tumor cells enhances PMN-MDSC-driven immunosuppression through the cGAS-STING pathway","authors":"Ping Lai, Lei Liu, Nicolò Bancaro, Martina Troiani, Bianca Calì, Yuxin Li, Jingjing Chen, Prafull Kumar Singh, Rydell Alvarez Arzola, Giuseppe Attanasio, Nicolò Pernigoni, Emiliano Pasquini, Simone Mosole, Andrea Rinaldi, Jacopo Sgrignani, Shi Qiu, Pan Song, Yingrui Li, Maria Andrea Desbats, Azucena Rendón Ángel, Andrea Alimonti","doi":"10.1016/j.immuni.2025.03.005","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.03.005","url":null,"abstract":"Mitochondrial dysfunction is a hallmark of cellular senescence. Here, we investigated whether senescent cells release mitochondrial (mt)DNA into the extracellular space and its impact on innate immunity. We found that both primary senescent cells and tumor cells undergoing therapy-induced senescence actively released mtDNA into the extracellular environment. mtDNA released by senescent cells was packaged within extracellular vesicles and selectively transferred to polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the tumor microenvironment. Upon uptake, extracellular mtDNA enhanced the immunosuppressive activity of PMN-MDSCs via cGAS-STING-NF-κB signaling, thereby promoting tumor progression. While STING activation directly induced NF-κB signaling, it also activated PKR-like endoplasmic reticulum kinase (PERK), which further amplified NF-κB activity, in PMN-MDSCs. mtDNA release from senescent cells was mediated by voltage-dependent anion channels (VDACs), and pharmacological inhibition of VDAC reduced extracellular mtDNA levels, reversed PMN-MDSC-driven immunosuppression, and enhanced chemotherapy efficacy in prostate cancer mouse models. These findings suggest that targeting mtDNA release could reprogram the immunosuppressive tumor microenvironment, improving therapeutic outcomes for chemotherapy-treated patients.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"34 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797997","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

Soluble CTLA-4 regulates immune homeostasis and promotes resolution of inflammation by suppressing type 1 but allowing type 2 immunity 可溶性CTLA-4调节免疫稳态，通过抑制1型而允许2型免疫来促进炎症的解决

IF 32.4 1区医学

Immunity Pub Date : 2025-03-31 DOI: 10.1016/j.immuni.2025.03.004

Motonao Osaki, Shimon Sakaguchi

{"title":"Soluble CTLA-4 regulates immune homeostasis and promotes resolution of inflammation by suppressing type 1 but allowing type 2 immunity","authors":"Motonao Osaki, Shimon Sakaguchi","doi":"10.1016/j.immuni.2025.03.004","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.03.004","url":null,"abstract":"Cytotoxic T-lymphocyte-associated antigen -4 (CTLA-4) is a co-inhibitory receptor that restricts T cell activation. CTLA-4 exists as membrane (mCTLA-4) and soluble (sCTLA-4) forms, but the key producers, kinetics, and functions of sCTLA-4 are unclear. Here, we investigated the roles of sCTLA-4 in immune regulation under non-inflammatory and inflammatory conditions. Effector regulatory T (Treg) cells were the most active sCTLA-4 producers in basal and inflammatory states, with distinct kinetics upon T cell receptor (TCR) stimulation. We generated mice specifically deficient in sCTLA-4 production, which exhibited spontaneous activation of type 1 immune cells and heightened autoantibody/immunoglobulin E (IgE) production. Conversely, mCTLA-4-deficient mice developed severe type 2-skewed autoimmunity. sCTLA-4 blockade of CD80/86 on antigen-presenting cells inhibited T helper (Th)1, but not Th2, differentiation <em>in vitro</em>. <em>In vivo</em>, Treg-produced sCTLA-4, suppressed Th1-mediated experimental colitis, and enhanced wound healing but hampered tumor immunity. Thus, sCTLA-4 is essential for immune homeostasis and controlling type 1 immunity while allowing type 2 immunity to facilitate resolution in inflammatory conditions.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"31 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736967","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

Immunological drivers of zoonotic virus emergence, evolution, and endemicity 人畜共患病毒出现、进化和地方性的免疫学驱动因素

IF 32.4 1区医学

Immunity Pub Date : 2025-03-31 DOI: 10.1016/j.immuni.2025.03.014

Jyothi N. Purushotham, Holly L. Lutz, Edyth Parker, Kristian G. Andersen

引用次数: 0

Diverse priming outcomes under conditions of very rare precursor B cells 在非常罕见的前体B细胞条件下，多种启动结果

IF 32.4 1区医学

Immunity Pub Date : 2025-03-31 DOI: 10.1016/j.immuni.2025.03.003

Patrick J. Madden, Ester Marina-Zárate, Kristen A. Rodrigues, Jon M. Steichen, Monolina Shil, Kaiyuan Ni, Katarzyna Kaczmarek Michaels, Laura Maiorino, Amit A. Upadhyay, Swati Saha, Arpan Pradhan, Oleksandr Kalyuzhiny, Alessia Liguori, Paul G. Lopez, Ivy Phung, Claudia Flynn, Amelia Zhou, Mariane B. Melo, Ashley Lemnios, Nicole Phelps, Shane Crotty

{"title":"Diverse priming outcomes under conditions of very rare precursor B cells","authors":"Patrick J. Madden, Ester Marina-Zárate, Kristen A. Rodrigues, Jon M. Steichen, Monolina Shil, Kaiyuan Ni, Katarzyna Kaczmarek Michaels, Laura Maiorino, Amit A. Upadhyay, Swati Saha, Arpan Pradhan, Oleksandr Kalyuzhiny, Alessia Liguori, Paul G. Lopez, Ivy Phung, Claudia Flynn, Amelia Zhou, Mariane B. Melo, Ashley Lemnios, Nicole Phelps, Shane Crotty","doi":"10.1016/j.immuni.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.03.003","url":null,"abstract":"Rare naive B cells have special pathogen-recognition features that enable outsized contributions to protective immunity but infrequently participate in immune responses. We investigatee how germline-targeting vaccine delivery and adjuvant selection affect priming of exceptionally rare BG18-like HIV broadly neutralizing antibody-precursor B cells (<1-in-50 million) in non-human primates. Only escalating dose (ED) priming immunization using the saponin adjuvant SMNP elicited detectable BG18-like cells in germinal centers (GCs) compared with other conditions. All groups had strong GC responses, but only ED+SMNP and bolus+SMNP induced BG18-like memory B cells in >50% of animals. One group had vaccine-specific GC responses equivalent to ED+SMNP but scarce BG18-like B cells. Following homologous boosting, BG18-like memory B cells were present in a bolus priming group but with lower somatic hypermutation and affinities than ED+SMNP. This outcome inversely associated with post-prime antibody titers, suggesting antibody feedback significantly influences rare precursor B cell responses. Thus, antigen and inflammatory stimuli extensively impact priming and affinity maturation of rare B cells.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"29 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736966","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

Tumor-derived arachidonic acid reprograms neutrophils to promote immune suppression and therapy resistance in triple-negative breast cancer 肿瘤来源的花生四烯酸重编程中性粒细胞，促进三阴性乳腺癌的免疫抑制和治疗抵抗

IF 32.4 1区医学

Immunity Pub Date : 2025-03-28 DOI: 10.1016/j.immuni.2025.03.002

Liqun Yu, Keziah Liebenberg, Yichao Shen, Fengshuo Liu, Zhan Xu, Xiaoxin Hao, Ling Wu, Weijie Zhang, Hilda L. Chan, Bo Wei, Philip L. Lorenzi, Yang Gao, Igor Bado, Luis Becerra-Dominguez, Charlotte Helena Rivas, Sergio Aguirre, Bradley C. Pingel, Yi-Hsuan Wu, Yunfeng Ding, Jun Liu, Xiang H.-F. Zhang

{"title":"Tumor-derived arachidonic acid reprograms neutrophils to promote immune suppression and therapy resistance in triple-negative breast cancer","authors":"Liqun Yu, Keziah Liebenberg, Yichao Shen, Fengshuo Liu, Zhan Xu, Xiaoxin Hao, Ling Wu, Weijie Zhang, Hilda L. Chan, Bo Wei, Philip L. Lorenzi, Yang Gao, Igor Bado, Luis Becerra-Dominguez, Charlotte Helena Rivas, Sergio Aguirre, Bradley C. Pingel, Yi-Hsuan Wu, Yunfeng Ding, Jun Liu, Xiang H.-F. Zhang","doi":"10.1016/j.immuni.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.03.002","url":null,"abstract":"The combination of immune checkpoint blockade and chemotherapies is the standard of care for triple-negative breast cancer (TNBC). However, initially, responsive tumors can still develop recurrences, suggesting acquired resistance mechanisms that remain poorly understood. Herein, we discover that TNBC cells surviving anti-programmed cell death protein-1 (anti-PD-1) and chemotherapy treatment accumulate neutral lipids. Disrupting lipid droplet formation in cancer cells reverses resistance and mitigates the immunosuppressive microenvironment. Single-cell RNA sequencing reveals a subset of neutrophils exhibiting a lipid-laden phenotype similar to adjacent tumor cells. Mechanistically, tumor-derived extracellular vesicles carrying lipids, including arachidonic acid (AA), mediate neutrophil reprogramming. Blocking dietary intake of omega-6 fatty acids or inhibiting fatty acid elongation for AA synthesis restores anti-tumor immunity and re-sensitizes the resistant tumors to anti-PD-1 and chemotherapy treatment. In human patients, AA metabolism-related pathways correlates with neutrophil enrichment. Overall, we demonstrate how lipid accumulation in TNBC cells leads to immune suppression and therapy resistance.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"13 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723819","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