Nature Immunology最新文献

Efficacy of CTLA-4 checkpoint therapy is dependent on IL-21 signaling to mediate cytotoxic reprogramming of PD-1+CD8+ T cells

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-12-19 DOI: 10.1038/s41590-024-02027-0

Zhen Zhang, Marlene Langenbach, Sagar Sagar, Viktor Fetsch, Jonas Stritzker, Elizabeth Severa, Ke Meng, Frances Winkler, Nisha Rana, Katharina Zoldan, Ira Godbole, Sabrina Solis, Jeffrey S. Weber, David Rafei-Shamsabadi, Saskia Lehr, Rebecca Diehl, Ana Cecilia Venhoff, Reinhard E. Voll, Nico Buettner, Christoph Neumann-Haefelin, Tobias Boettler, Maike Hofmann, Melanie Boerries, Frank Meiss, Robert Zeiser, Robert Thimme, Ramin S. Herati, Bertram Bengsch

{"title":"Efficacy of CTLA-4 checkpoint therapy is dependent on IL-21 signaling to mediate cytotoxic reprogramming of PD-1+CD8+ T cells","authors":"Zhen Zhang, Marlene Langenbach, Sagar Sagar, Viktor Fetsch, Jonas Stritzker, Elizabeth Severa, Ke Meng, Frances Winkler, Nisha Rana, Katharina Zoldan, Ira Godbole, Sabrina Solis, Jeffrey S. Weber, David Rafei-Shamsabadi, Saskia Lehr, Rebecca Diehl, Ana Cecilia Venhoff, Reinhard E. Voll, Nico Buettner, Christoph Neumann-Haefelin, Tobias Boettler, Maike Hofmann, Melanie Boerries, Frank Meiss, Robert Zeiser, Robert Thimme, Ramin S. Herati, Bertram Bengsch","doi":"10.1038/s41590-024-02027-0","DOIUrl":"https://doi.org/10.1038/s41590-024-02027-0","url":null,"abstract":"The mechanisms underlying the efficacy of anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) therapy are incompletely understood. Here, by immune profiling responding PD-1+CD8+ T (TResp) cell populations from patients with advanced melanoma, we identified differential programming of TResp cells in response to combination therapy, from an exhausted toward a more cytotoxic effector program. This effect does not occur with anti-PD-1 monotherapy. Single-cell transcriptome and T cell receptor repertoire analysis was used to identify altered effector programming of expanding PD-1+CD8+ T cell clones with distinct regulon usage, STAT1 and STAT3 utilization and antitumor specificity connected to interleukin (IL)-21 signaling in combination and anti-CTLA-4 monotherapy. Therapeutic efficacy of CTLA-4 blockade was lost in B16F10 melanoma models with either Il21r− deficiency or anti-IL-21 receptor blockade. Together, these results show how IL-21 signaling to TResp is critical for anti-CTLA-4-based checkpoint therapies and highlight major signaling differences to anti-PD-1 monotherapy.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"11 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849137","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

Pyroptotic corpses are flagged by filopodia to alert dendritic cells

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-12-12 DOI: 10.1038/s41590-024-02025-2

引用次数: 0

Pyroptotic cell corpses are crowned with F-actin-rich filopodia that engage CLEC9A signaling in incoming dendritic cells

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-12-04 DOI: 10.1038/s41590-024-02024-3

Caroline L. Holley, Mercedes Monteleone, Daniel Fisch, Alexandre E. S. Libert, Robert J. Ju, Joon H. Choi, Nicholas D. Condon, Stefan Emming, Joanna Crawford, Grace M. E. P. Lawrence, Jared R. Coombs, James G. Lefevre, Rinie Bajracharya, Mireille H. Lahoud, Alpha S. Yap, Nicholas Hamilton, Samantha J. Stehbens, Jonathan C. Kagan, Nicholas Ariotti, Sabrina S. Burgener, Kate Schroder

{"title":"Pyroptotic cell corpses are crowned with F-actin-rich filopodia that engage CLEC9A signaling in incoming dendritic cells","authors":"Caroline L. Holley, Mercedes Monteleone, Daniel Fisch, Alexandre E. S. Libert, Robert J. Ju, Joon H. Choi, Nicholas D. Condon, Stefan Emming, Joanna Crawford, Grace M. E. P. Lawrence, Jared R. Coombs, James G. Lefevre, Rinie Bajracharya, Mireille H. Lahoud, Alpha S. Yap, Nicholas Hamilton, Samantha J. Stehbens, Jonathan C. Kagan, Nicholas Ariotti, Sabrina S. Burgener, Kate Schroder","doi":"10.1038/s41590-024-02024-3","DOIUrl":"https://doi.org/10.1038/s41590-024-02024-3","url":null,"abstract":"While apoptosis dismantles the cell to enforce immunological silence, pyroptotic cell death provokes inflammation. Little is known of the structural architecture of cells undergoing pyroptosis, and whether pyroptotic corpses are immunogenic. Here we report that inflammasomes trigger the Gasdermin-D- and calcium-dependent eruption of filopodia from the plasma membrane minutes before pyroptotic cell rupture, to crown the resultant corpse with filopodia. As a rich store of F-actin, pyroptotic filopodia are recognized by dendritic cells through the F-actin receptor, CLEC9A (DNGR1). We propose that cells assemble filopodia before cell rupture to serve as a posthumous mark for a cell that has died by gasdermin-induced pyroptosis, or MLKL-induced necroptosis, for recognition by dendritic cells. This study reveals the spectacular morphology of pyroptosis and identifies a mechanism by which inflammasomes induce pyroptotic cells to construct a de novo alarmin that activates dendritic cells via CLEC9A, which coordinates the transition from innate to adaptive immunity1,2.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"7 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763214","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

Author Correction: Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-12-02 DOI: 10.1038/s41590-024-02046-x

Ruoyan Li, Johanna Strobl, Elizabeth F. M. Poyner, Aya Balbaa, Fereshteh Torabi, Pavel V. Mazin, Nana-Jane Chipampe, Emily Stephenson, Ciro Ramírez-Suástegi, Vijaya Baskar Mahalingam Shanmugiah, Louis Gardner, Bayanne Olabi, Rowen Coulthard, Rachel A. Botting, Nina Zila, Elena Prigmore, Nusayhah H. Gopee, Marta A. Chroscik, Efpraxia Kritikaki, Justin Engelbert, Issac Goh, Hon Man Chan, Harriet F. Johnson, Jasmine Ellis, Victoria Rowe, Win Tun, Gary Reynolds, Dexin Yang, April Rose Foster, Laure Gambardella, Elena Winheim, Chloe Admane, Benjamin Rumney, Lloyd Steele, Laura Jardine, Julia Nenonen, Keir Pickard, Jennifer Lumley, Philip Hampton, Simeng Hu, Fengjie Liu, Xiangjun Liu, David Horsfall, Daniela Basurto-Lozada, Louise Grimble, Chris M. Bacon, Sophie C. Weatherhead, Hanna Brauner, Yang Wang, Fan Bai, Nick J. Reynolds, Judith E. Allen, Constanze Jonak, Patrick M. Brunner, Sarah A. Teichmann, Muzlifah Haniffa

引用次数: 0

Publisher Correction: Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-12-02 DOI: 10.1038/s41590-024-02045-y

Caterina E. Faliti, Trinh T. P. Van, Fabliha A. Anam, Narayanaiah Cheedarla, M. Elliott Williams, Ashish Kumar Mishra, Sabeena Y. Usman, Matthew C. Woodruff, Geoff Kraker, Martin C. Runnstrom, Shuya Kyu, Daniel Sanz, Hasan Ahmed, Midushi Ghimire, Andrea Morrison-Porter, Hannah Quehl, Natalie S. Haddad, Weirong Chen, Suneethamma Cheedarla, Andrew S. Neish, John D. Roback, Rustom Antia, Jennifer Hom, Christopher M. Tipton, John M. Lindner, Eliver Ghosn, Surender Khurana, Christopher D. Scharer, Arezou Khosroshahi, F. Eun-Hyung Lee, Ignacio Sanz

引用次数: 0

Circulating tumor-reactive KIR+CD8+ T cells suppress anti-tumor immunity in patients with melanoma 循环中的肿瘤反应性 KIR+CD8+ T 细胞抑制黑色素瘤患者的抗肿瘤免疫力

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-11-28 DOI: 10.1038/s41590-024-02023-4

Benjamin Y. Lu, Liliana E. Lucca, Wesley Lewis, Jiping Wang, Catarina V. Nogueira, Sebastian Heer, Violeta Rayon-Estrada, Pierre-Paul Axisa, Sarah M. Reeves, Nicholas C. Buitrago-Pocasangre, Giang H. Pham, Mina L. Kojima, Wei Wei, Lilach Aizenbud, Antonietta Bacchiocchi, Lin Zhang, Joseph J. Walewski, Veronica Chiang, Kelly Olino, James Clune, Ruth Halaban, Yuval Kluger, Anthony J. Coyle, Jan Kisielow, Franz-Josef Obermair, Harriet M. Kluger, David A. Hafler

{"title":"Circulating tumor-reactive KIR+CD8+ T cells suppress anti-tumor immunity in patients with melanoma","authors":"Benjamin Y. Lu, Liliana E. Lucca, Wesley Lewis, Jiping Wang, Catarina V. Nogueira, Sebastian Heer, Violeta Rayon-Estrada, Pierre-Paul Axisa, Sarah M. Reeves, Nicholas C. Buitrago-Pocasangre, Giang H. Pham, Mina L. Kojima, Wei Wei, Lilach Aizenbud, Antonietta Bacchiocchi, Lin Zhang, Joseph J. Walewski, Veronica Chiang, Kelly Olino, James Clune, Ruth Halaban, Yuval Kluger, Anthony J. Coyle, Jan Kisielow, Franz-Josef Obermair, Harriet M. Kluger, David A. Hafler","doi":"10.1038/s41590-024-02023-4","DOIUrl":"https://doi.org/10.1038/s41590-024-02023-4","url":null,"abstract":"Effective anti-tumor immunity is driven by cytotoxic CD8+ T cells with specificity for tumor antigens. However, the factors that control successful tumor rejection are not well understood. Here we identify a subpopulation of CD8+ T cells that are tumor-antigen-specific and can be identified by KIR expression but paradoxically impair anti-tumor immunity in patients with melanoma. These tumor-antigen-specific KIR+CD8+ regulatory T cells target other tumor-antigen-specific CD8+ T cells, can be detected in both the tumor and the blood, have a conserved transcriptional program and are associated with a poor overall survival. These findings broaden our understanding of the transcriptional and functional heterogeneity of human CD8+ T cells and implicate KIR+CD8+ regulatory T cells as a cellular mediator of immune evasion in human cancer.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"9 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735577","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

Macrophages and nociceptor neurons form a sentinel unit around fenestrated capillaries to defend the synovium from circulating immune challenge 巨噬细胞和痛觉神经元在栅栏状毛细血管周围形成一个哨兵单位，保护滑膜免受循环免疫的挑战

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-11-25 DOI: 10.1038/s41590-024-02011-8

Tetsuo Hasegawa, Colin Y. C. Lee, Andrew J. Hotchen, Aaron Fleming, Rahul Singh, Kunimichi Suzuki, Michisuke Yuzaki, Masahiko Watanabe, Mark A. Birch, Andrew W. McCaskie, Nikolett Lénárt, Krisztina Tóth, Ádám Dénes, Zhaoyuan Liu, Florent Ginhoux, Nathan Richoz, Menna R. Clatworthy

{"title":"Macrophages and nociceptor neurons form a sentinel unit around fenestrated capillaries to defend the synovium from circulating immune challenge","authors":"Tetsuo Hasegawa, Colin Y. C. Lee, Andrew J. Hotchen, Aaron Fleming, Rahul Singh, Kunimichi Suzuki, Michisuke Yuzaki, Masahiko Watanabe, Mark A. Birch, Andrew W. McCaskie, Nikolett Lénárt, Krisztina Tóth, Ádám Dénes, Zhaoyuan Liu, Florent Ginhoux, Nathan Richoz, Menna R. Clatworthy","doi":"10.1038/s41590-024-02011-8","DOIUrl":"10.1038/s41590-024-02011-8","url":null,"abstract":"A wide variety of systemic pathologies, including infectious and autoimmune diseases, are accompanied by joint pain or inflammation, often mediated by circulating immune complexes (ICs). How such stimuli access joints and trigger inflammation is unclear. Whole-mount synovial imaging revealed PV1+ fenestrated capillaries at the periphery of the synovium in the lining–sublining interface. Circulating ICs extravasated from these PV1+ capillaries, and nociceptor neurons and three distinct macrophage subsets formed a sentinel unit around them. Macrophages showed subset-specific responses to systemic IC challenge; LYVE1+CX3CR1+ macrophages orchestrated neutrophil recruitment and activated calcitonin gene-related peptide+ (CGRP+) nociceptor neurons via interleukin-1β. In contrast, major histocompatibility complex class II+CD11c+ (MHCII+CD11c+) and MHCII+CD11c– interstitial macrophages formed tight clusters around PV1+ capillaries in response to systemic immune stimuli, a feature enhanced by nociceptor-derived CGRP. Altogether, we identify the anatomical location of synovial PV1+ capillaries and subset-specific macrophage–nociceptor cross-talk that forms a blood–joint barrier protecting the synovium from circulating immune challenges. Why joints are highly responsive to systemic inflammation is unknown. Hasegawa et al. sought to address this question, developing a whole-mount imaging system of the entire synovium to profile the vascular, neuronal and immune components.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 12","pages":"2270-2283"},"PeriodicalIF":27.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-02011-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713105","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-4 promotes immunotherapy resistance IL-4 促进免疫疗法的抗药性

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-11-25 DOI: 10.1038/s41590-024-02032-3

Paula Jauregui

引用次数: 0

The brain tames autoimmunity 大脑驯服自身免疫

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-11-25 DOI: 10.1038/s41590-024-02033-2

Nicholas J. Bernard

引用次数: 0

Next-generation combination approaches for immune checkpoint therapy 免疫检查点疗法的新一代组合方法

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-11-25 DOI: 10.1038/s41590-024-02015-4

Sangeeta Goswami, Kristen E. Pauken, Linghua Wang, Padmanee Sharma

{"title":"Next-generation combination approaches for immune checkpoint therapy","authors":"Sangeeta Goswami, Kristen E. Pauken, Linghua Wang, Padmanee Sharma","doi":"10.1038/s41590-024-02015-4","DOIUrl":"10.1038/s41590-024-02015-4","url":null,"abstract":"Immune checkpoint therapy has revolutionized cancer treatment, leading to dramatic clinical outcomes for a subset of patients. However, many patients do not experience durable responses following immune checkpoint therapy owing to multiple resistance mechanisms, highlighting the need for effective combination strategies that target these resistance pathways and improve clinical responses. The development of combination strategies based on an understanding of the complex biology that regulates human antitumor immune responses has been a major challenge. In this Review, we describe the current landscape of combination therapies. We also discuss how the development of effective combination strategies will require the integration of small, tissue-rich clinical trials, to determine how therapy-driven perturbation of the human immune system affects downstream biological responses and eventual clinical outcomes, reverse translation of clinical observations to immunocompetent preclinical models, to interrogate specific biological pathways and their impact on antitumor immune responses, and novel computational methods and machine learning, to integrate multiple datasets across clinical and preclinical studies for the identification of the most relevant pathways that need to be targeted for successful combination strategies. In this Review, Sharma and colleagues describe the current landscape of combination therapies and discuss requirements for the development of effective combination strategies.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 12","pages":"2186-2199"},"PeriodicalIF":27.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713361","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