Pub Date : 2025-10-31DOI: 10.1016/j.immuni.2025.10.013
Kevin Bi, Soki Kashima, Sabrina Y. Camp, Kevin Meli, Eddy Saad, Breanna M. Titchen, Chris Labaki, Ziad Bakouny, Erica M. Pimenta, Jihye Park, Erin Shannon, Jingxin Fu, Sherin Xirenayi, Jack Horst, Lotus Lum, Jeffrey J. Ishizuka, Toni K. Choueiri, David A. Braun, Eliezer M. Van Allen
Sustained type-I and type-II interferon (IFN) signaling can drive multiple mechanisms of resistance to immune checkpoint blockade (ICB). Here, we used single-cell RNA sequencing data to characterize the effects of IFNs in the tumor-immune microenvironment (TME) of renal cell carcinoma (RCC) and then examined how IFN-driven cellular phenotypes modulate ICB efficacy. Using mixed-effects models, we inferred the IFN inducibility of putative IFN-stimulated genes (ISGs) within cell types. Genes encoding inhibitory ligands and immune checkpoints were strongly expressed and IFN inducible in macrophages but less so in RCC tumor cells. In orthogonal clinical trial cohorts, a signature of myeloid IFNγ signaling, but not tumor IFNγ signaling, predicted primary resistance to first-line ICB plus anti-VEGF therapy. Functionally, IFNγ-conditioned macrophages inhibited T cell killing of RCC tumor cells in vitro. Our inferential modeling approach offers a framework for biomarker discovery through deconvolution of cytokine signaling effects in the TME and points to myeloid cells as mediators of tumor-extrinsic, IFN-driven resistance to immunotherapy in RCC.
{"title":"Myeloid cells mediate interferon-driven resistance to immunotherapy in advanced renal cell carcinoma","authors":"Kevin Bi, Soki Kashima, Sabrina Y. Camp, Kevin Meli, Eddy Saad, Breanna M. Titchen, Chris Labaki, Ziad Bakouny, Erica M. Pimenta, Jihye Park, Erin Shannon, Jingxin Fu, Sherin Xirenayi, Jack Horst, Lotus Lum, Jeffrey J. Ishizuka, Toni K. Choueiri, David A. Braun, Eliezer M. Van Allen","doi":"10.1016/j.immuni.2025.10.013","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.10.013","url":null,"abstract":"Sustained type-I and type-II interferon (IFN) signaling can drive multiple mechanisms of resistance to immune checkpoint blockade (ICB). Here, we used single-cell RNA sequencing data to characterize the effects of IFNs in the tumor-immune microenvironment (TME) of renal cell carcinoma (RCC) and then examined how IFN-driven cellular phenotypes modulate ICB efficacy. Using mixed-effects models, we inferred the IFN inducibility of putative IFN-stimulated genes (ISGs) within cell types. Genes encoding inhibitory ligands and immune checkpoints were strongly expressed and IFN inducible in macrophages but less so in RCC tumor cells. In orthogonal clinical trial cohorts, a signature of myeloid IFNγ signaling, but not tumor IFNγ signaling, predicted primary resistance to first-line ICB plus anti-VEGF therapy. Functionally, IFNγ-conditioned macrophages inhibited T cell killing of RCC tumor cells <em>in vitro</em>. Our inferential modeling approach offers a framework for biomarker discovery through deconvolution of cytokine signaling effects in the TME and points to myeloid cells as mediators of tumor-extrinsic, IFN-driven resistance to immunotherapy in RCC.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"15 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145403932","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}
Pub Date : 2025-10-30DOI: 10.1016/j.immuni.2025.10.005
Joseph Léger, Eva Artano, Delphine Coulais, Naomie Belletoise, Raoudha Fadhloun, Devin Kenney, Avinash Bhandoola, Christelle Harly
Understanding the mechanisms that initiate innate lymphoid cell (ILC) specification may reveal how ILC functions in immunity and tissue homeostasis are programmed. Using an Il7r-lineage tracing mouse strain, we identified developmental intermediates between lymphoid progenitors and Tcf7+ ILC progenitors in the mouse bone marrow (BM). Transcriptional analysis of these intermediates identified very early expression of the transcription factor nuclear factor, interleukin 3 regulated (NFIL3). Nfil3−/− mice lacked all BM ILC-specified precursors. Forced expression of NFIL3 in lymphoid progenitors induced Tcf7+ ILC-lineage cells capable of generating all ILC subsets and conventional natural killer cells. Transient activity of NFIL3 in lymphoid precursors recapitulated BM ILC development in vitro, leading to the generation of all adult ILCs. Mechanistically, NFIL3 initiated ILC specification by inducing expression of key transcriptional regulators of ILC development—Tox, Id2, Gata3, Tcf7, and Zbtb16. Our findings indicate an apex role for NFIL3 in ILC specification and provide an in vitro approach to generate ILC-lineage cells with potential therapeutic utility.
{"title":"The transcription factor NFIL3 drives innate lymphoid cell specification from lymphoid progenitors","authors":"Joseph Léger, Eva Artano, Delphine Coulais, Naomie Belletoise, Raoudha Fadhloun, Devin Kenney, Avinash Bhandoola, Christelle Harly","doi":"10.1016/j.immuni.2025.10.005","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.10.005","url":null,"abstract":"Understanding the mechanisms that initiate innate lymphoid cell (ILC) specification may reveal how ILC functions in immunity and tissue homeostasis are programmed. Using an <em>Il7r</em>-lineage tracing mouse strain, we identified developmental intermediates between lymphoid progenitors and <em>Tcf7</em><sup><em>+</em></sup> ILC progenitors in the mouse bone marrow (BM). Transcriptional analysis of these intermediates identified very early expression of the transcription factor nuclear factor, interleukin 3 regulated (NFIL3). <em>Nfil3</em><sup>−/−</sup> mice lacked all BM ILC-specified precursors. Forced expression of NFIL3 in lymphoid progenitors induced <em>Tcf7</em><sup><em>+</em></sup> ILC-lineage cells capable of generating all ILC subsets and conventional natural killer cells. Transient activity of NFIL3 in lymphoid precursors recapitulated BM ILC development <em>in vitro</em>, leading to the generation of all adult ILCs. Mechanistically, NFIL3 initiated ILC specification by inducing expression of key transcriptional regulators of ILC development—<em>Tox</em>, <em>Id2</em>, <em>Gata3</em>, <em>Tcf7</em>, and <em>Zbtb16</em>. Our findings indicate an apex role for NFIL3 in ILC specification and provide an <em>in vitro</em> approach to generate ILC-lineage cells with potential therapeutic utility.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"46 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145397591","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}
Pub Date : 2025-10-29DOI: 10.1016/j.immuni.2025.10.003
Ruoqing Feng, Lena Spieth, Lu Liu, Stefan Berghoff, Jonas Franz, Qian Liu, Zhen Wang, Vini Tiwari, Simona Vitale, Simon Frerich, Sergi Florensa, Niklas Junker, Ludwig Huber, Marco Keller, Christoph Müller, Franz Bracher, Xiaoke Ge, Patrick C.N. Rensen, Gijs Kooij, Leon Hosang, Serhii Chornyi, Martin Dichgans, Ozgun Gokce, Gesine Saher, Christine Stadelmann, Martin Giera, Janos Groh, Mikael Simons
{"title":"Single-cell spatial transcriptomic profiling defines a pathogenic inflammatory niche in chronic active multiple sclerosis lesions","authors":"Ruoqing Feng, Lena Spieth, Lu Liu, Stefan Berghoff, Jonas Franz, Qian Liu, Zhen Wang, Vini Tiwari, Simona Vitale, Simon Frerich, Sergi Florensa, Niklas Junker, Ludwig Huber, Marco Keller, Christoph Müller, Franz Bracher, Xiaoke Ge, Patrick C.N. Rensen, Gijs Kooij, Leon Hosang, Serhii Chornyi, Martin Dichgans, Ozgun Gokce, Gesine Saher, Christine Stadelmann, Martin Giera, Janos Groh, Mikael Simons","doi":"10.1016/j.immuni.2025.10.003","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.10.003","url":null,"abstract":"","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"138 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145383256","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}
Pub Date : 2025-10-14DOI: 10.1016/j.immuni.2025.09.015
Zhaoyu Lin, Hai-Bin Ruan
Membrane targeting and pore formation of gasdermin C are facilitated by its proteolytic cleavage. In this issue of Immunity, Pandey et al. show how cathepsin S cleaves intestinal epithelial gasdermin C to amplify type 2 immune responses.
{"title":"Cutting the Gordian knot: Untangling gasdermin C from pyroptosis","authors":"Zhaoyu Lin, Hai-Bin Ruan","doi":"10.1016/j.immuni.2025.09.015","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.09.015","url":null,"abstract":"Membrane targeting and pore formation of gasdermin C are facilitated by its proteolytic cleavage. In this issue of <em>Immunity</em>, Pandey et al. show how cathepsin S cleaves intestinal epithelial gasdermin C to amplify type 2 immune responses.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"24 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283463","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}
Pub Date : 2025-10-14DOI: 10.1016/j.immuni.2025.09.017
Sigrun Stulz, Georg Gasteiger
Vaccines that induce immunity in tissues are urgently needed. In this issue of Immunity, Joag et al. demonstrate that systemic vaccination of primates induces tissue-resident CD8+ T cells in numerous organs that can activate antiviral responses by stromal, parenchymal, and immune cells.
{"title":"Resident memory T cells call the shots in tissue immunity","authors":"Sigrun Stulz, Georg Gasteiger","doi":"10.1016/j.immuni.2025.09.017","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.09.017","url":null,"abstract":"Vaccines that induce immunity in tissues are urgently needed. In this issue of <em>Immunity</em>, Joag et al. demonstrate that systemic vaccination of primates induces tissue-resident CD8<sup>+</sup> T cells in numerous organs that can activate antiviral responses by stromal, parenchymal, and immune cells.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"11 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283465","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}
Pub Date : 2025-10-14DOI: 10.1016/j.immuni.2025.09.010
Jake A. Gertie, Hachung Chung
Neuroinflammation contributes to Alzheimer’s disease (AD), but the molecules and pathways that initiate inflammation are unclear. In this issue of Immunity, Song et al. demonstrate that ZBP1-RIPK1 signaling in microglia can drive AD, wherein ZBP1 is activated by left-handed Z-DNA leaking from mitochondria, presenting new molecular targets for AD therapeutics.
{"title":"Alzheimer’s alphabet soup: Find the letters “Z-DNA-ZBP1-RIPK1”","authors":"Jake A. Gertie, Hachung Chung","doi":"10.1016/j.immuni.2025.09.010","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.09.010","url":null,"abstract":"Neuroinflammation contributes to Alzheimer’s disease (AD), but the molecules and pathways that initiate inflammation are unclear. In this issue of <em>Immunity</em>, Song et al. demonstrate that ZBP1-RIPK1 signaling in microglia can drive AD, wherein ZBP1 is activated by left-handed Z-DNA leaking from mitochondria, presenting new molecular targets for AD therapeutics.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"43 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283468","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}
Pub Date : 2025-10-14DOI: 10.1016/j.immuni.2025.09.005
Adrian Straub, Zahra Abedi, Dirk H. Busch, Veit R. Buchholz
Section snippets
Main text
Abdullah et al.1 recently set out to gauge the influence of T cell receptor (TCR)-intrinsic vs. -extrinsic factors on memory vs. effector fate decisions of CD8+ T cells. They concluded that “a majority of TCR clonotypes were highly biased toward memory or effector fate,” and that “TCR intrinsic biases […] were dominant over environmental cues.” We argue that these conclusions cannot be drawn based on the authors’ limited clonotypic data and are strongly opposed by our own observation of highly
Acknowledgments
The ultra-deep H2-Kb/SIINFEKL-specific TCR library was created as part of the MATCHMAKERS team, supported by the Cancer Grand Challenges partnership financed by CRUK (CGCATF-2023/100002) and the National Cancer Institute (1OT2CA297204-01). A.S., Z.A., and D.H.B. are members of the MATCHMAKERS team. The work was further funded by SFB-TRR 338/1 2021- 452881907 (project A01 [D.H.B.] and project B02 [V.R.B.]) and the European Research Council (starting grant 949719 SCIMAP to V.R.B.).
{"title":"Nurture over nature in fate decisions of antigen-specific CD8+ T cell clones from an endogenous repertoire","authors":"Adrian Straub, Zahra Abedi, Dirk H. Busch, Veit R. Buchholz","doi":"10.1016/j.immuni.2025.09.005","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.09.005","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>Abdullah et al.<sup>1</sup> recently set out to gauge the influence of T cell receptor (TCR)-intrinsic vs. -extrinsic factors on memory vs. effector fate decisions of CD8<sup>+</sup> T cells. They concluded that “a majority of TCR clonotypes were highly biased toward memory or effector fate,” and that “TCR intrinsic biases […] were dominant over environmental cues.” We argue that these conclusions cannot be drawn based on the authors’ limited clonotypic data and are strongly opposed by our own observation of highly</section></section><section><section><h2>Acknowledgments</h2>The ultra-deep H2-K<sup>b</sup>/SIINFEKL-specific TCR library was created as part of the MATCHMAKERS team, supported by the Cancer Grand Challenges partnership financed by <span>CRUK</span> (CGCATF-2023/100002) and the <span>National Cancer Institute</span> (1OT2CA297204-01). A.S., Z.A., and D.H.B. are members of the MATCHMAKERS team. The work was further funded by SFB-TRR 338/1 2021- 452881907 (project A01 [D.H.B.] and project B02 [V.R.B.]) and the <span>European Research Council</span> (starting grant 949719 SCIMAP to V.R.B.).</section></section><section><section><h2>Declaration of interests</h2>The authors declare no competing interests.</section></section>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"81 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283462","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}
Pub Date : 2025-10-14DOI: 10.1016/j.immuni.2025.09.009
Vineet Joag, Benjamin N. Bimber, Clare F. Quarnstrom, Venkata S. Bollimpelli, Jason M. Schenkel, Kathryn A. Fraser, Mario Bertogliat, Andrew G. Soerens, J. Michael Stolley, Stephen D. O’Flanagan, Pamela C. Rosato, Noah V. Gavil, Marco Künzli, Jason S. Mitchell, Traci Legere, Sherrie Jean, Amit A. Upadhyay, C. Yong Kang, James Gibbs, Jonathan W. Yewdell, David Masopust
CD8+ resident memory T (Trm) cells comprise a small population of frontline sentinels compared with the large tissues they surveil, making outsized contributions to immune protection from infection. Here, we interrogated mechanisms of Trm cell function in primates. Intravenous immunization of macaques with a simian immunodeficiency virus (SIV)-gag-containing heterologous prime-boost-boost vaccine established memory T cells in >30 tissues, including visceral and mucosal compartments. Upon in vivo reactivation in the reproductive tract, antigen-sensing CD8+ Trm activated local stromal, parenchymal, and innate and adaptive immune cells. Stromal and parenchymal cells accentuated leukocyte migration and antiviral defenses. B and plasma cells mobilized into the vaginal mucosa, and bloodborne CD4+ T cells were recruited and adopted a host-defense program. Our findings demonstrate that systemic vaccination promotes a Trm cell response in barrier compartments and that Trm cells repurpose abundant neighboring stromal, parenchymal, and immune cells to amplify alarm signals and activate diverse host defenses.
{"title":"Primate resident memory T cells activate humoral and stromal immunity","authors":"Vineet Joag, Benjamin N. Bimber, Clare F. Quarnstrom, Venkata S. Bollimpelli, Jason M. Schenkel, Kathryn A. Fraser, Mario Bertogliat, Andrew G. Soerens, J. Michael Stolley, Stephen D. O’Flanagan, Pamela C. Rosato, Noah V. Gavil, Marco Künzli, Jason S. Mitchell, Traci Legere, Sherrie Jean, Amit A. Upadhyay, C. Yong Kang, James Gibbs, Jonathan W. Yewdell, David Masopust","doi":"10.1016/j.immuni.2025.09.009","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.09.009","url":null,"abstract":"CD8<sup>+</sup> resident memory T (Trm) cells comprise a small population of frontline sentinels compared with the large tissues they surveil, making outsized contributions to immune protection from infection. Here, we interrogated mechanisms of Trm cell function in primates. Intravenous immunization of macaques with a simian immunodeficiency virus (SIV)-gag-containing heterologous prime-boost-boost vaccine established memory T cells in >30 tissues, including visceral and mucosal compartments. Upon <em>in vivo</em> reactivation in the reproductive tract, antigen-sensing CD8<sup>+</sup> Trm activated local stromal, parenchymal, and innate and adaptive immune cells. Stromal and parenchymal cells accentuated leukocyte migration and antiviral defenses. B and plasma cells mobilized into the vaginal mucosa, and bloodborne CD4<sup>+</sup> T cells were recruited and adopted a host-defense program. Our findings demonstrate that systemic vaccination promotes a Trm cell response in barrier compartments and that Trm cells repurpose abundant neighboring stromal, parenchymal, and immune cells to amplify alarm signals and activate diverse host defenses.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"120 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283789","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}
Pub Date : 2025-10-14DOI: 10.1016/j.immuni.2025.09.006
Leena Abdullah, Joshua J. Obar, Yina H. Huang
Section snippets
Main text
Upon activation, individual CD8+ clones decide between effector and memory T cell fates by integrating intrinsic T cell receptor (TCR) signals or “nature” and extrinsic signals from co-stimulatory ligands and inflammatory cytokines or “nurture”. The collective antigen-specific CD8+ T cell response is composed of differential fate decisions made by ∼100–1,000 individual clones. Several models describe how variations in nature drive effector vs. memory T cell differentiation, including the
Acknowledgments
This work was supported in part by the National Institutes of Health (NIH) grant R01-AI131975 to Y.H.H.; Tom and Susan Stepp to Y.H.H.; Prouty Developmental grant to Y.H.H.; NIH grants P20-GM130454, S10-OD025235, and S10-OD030242, which support the single-cell genomics core; and NIH grant P30-CA023108, which supports the Dartmouth Cancer Center’s flow cytometry (RRID: SCR_019165) and genomics (RRID: SCR_021293) shared resources.
Author contributions
L.A. and Y.H.H. wrote the original manuscript. J.J.O. provided feedback on the final manuscript.
{"title":"Reply to nurture over nature in fate decisions of antigen-specific CD8+ T cell clones from an endogenous repertoire","authors":"Leena Abdullah, Joshua J. Obar, Yina H. Huang","doi":"10.1016/j.immuni.2025.09.006","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.09.006","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>Upon activation, individual CD8<sup>+</sup> clones decide between effector and memory T cell fates by integrating intrinsic T cell receptor (TCR) signals or “nature” and extrinsic signals from co-stimulatory ligands and inflammatory cytokines or “nurture”. The collective antigen-specific CD8<sup>+</sup> T cell response is composed of differential fate decisions made by ∼100–1,000 individual clones. Several models describe how variations in nature drive effector vs. memory T cell differentiation, including the</section></section><section><section><h2>Acknowledgments</h2>This work was supported in part by the <span>National Institutes of Health</span> (NIH) grant <!-- -->R01-AI131975<!-- --> to Y.H.H.; Tom and Susan Stepp to Y.H.H.; <span>Prouty Developmental grant</span> to Y.H.H.; <span>NIH</span> grants <!-- -->P20-GM130454<!-- -->, <!-- -->S10-OD025235<!-- -->, and <!-- -->S10-OD030242<!-- -->, which support the single-cell genomics core; and <span>NIH</span> grant <!-- -->P30-CA023108<!-- -->, which supports the <span>Dartmouth Cancer Center’s flow cytometry</span> (RRID: <span>SCR_019165</span>) and genomics (RRID: <span>SCR_021293</span>) shared resources.</section></section><section><section><h2>Author contributions</h2>L.A. and Y.H.H. wrote the original manuscript. J.J.O. provided feedback on the final manuscript.</section></section><section><section><h2>Declaration of interests</h2>The authors declare no competing interests.</section></section>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"3 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283466","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}
Pub Date : 2025-10-14DOI: 10.1016/j.immuni.2025.09.016
Alexander J. Wesolowski, Rahul Roychoudhuri
T cells need reactive oxygen species (ROS) for activation and memory formation, yet excessive ROS can drive dysfunction. Rivadeneira et al. show that chronic T cell activation in tumors exposes telomeres to damaging mitochondrial ROS, contributing to T cell dysfunction.
{"title":"Burning the candle at both ends: ROS-mediated telomere damage drives T cell dysfunction","authors":"Alexander J. Wesolowski, Rahul Roychoudhuri","doi":"10.1016/j.immuni.2025.09.016","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.09.016","url":null,"abstract":"T cells need reactive oxygen species (ROS) for activation and memory formation, yet excessive ROS can drive dysfunction. Rivadeneira et al. show that chronic T cell activation in tumors exposes telomeres to damaging mitochondrial ROS, contributing to T cell dysfunction.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"19 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283464","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：