Sai Xiao, Shoubao Ma, Baofa Sun, Wenchen Pu, Songqi Duan, Jingjing Han, Yaqun Hong, Jianying Zhang, Yong Peng, Chuan He, Ping Yi, Michael A. Caligiuri, Jianhua Yu
{"title":"The tumor-intrinsic role of the m6A reader YTHDF2 in regulating immune evasion","authors":"Sai Xiao, Shoubao Ma, Baofa Sun, Wenchen Pu, Songqi Duan, Jingjing Han, Yaqun Hong, Jianying Zhang, Yong Peng, Chuan He, Ping Yi, Michael A. Caligiuri, Jianhua Yu","doi":"10.1126/sciimmunol.adl2171","DOIUrl":"10.1126/sciimmunol.adl2171","url":null,"abstract":"<div >Tumors evade attacks from the immune system through various mechanisms. Here, we identify a component of tumor immune evasion mediated by YTH domain–containing family protein 2 (YTHDF2), a reader protein that usually destabilizes m<sup>6</sup>A-modified mRNA. Loss of tumoral YTHDF2 inhibits tumor growth and prolongs survival in immunocompetent tumor models. Mechanistically, tumoral YTHDF2 deficiency promotes the recruitment of macrophages via CX3CL1 and enhances mitochondrial respiration of CD8<sup>+</sup> T cells by impairing tumor glycolysis metabolism. Tumoral YTHDF2 deficiency promotes inflammatory macrophage polarization and antigen presentation in the presence of IFN-γ. In addition, IFN-γ induces autophagic degradation of tumoral YTHDF2, thereby sensitizing tumor cells to CD8<sup>+</sup> T cell–mediated cytotoxicity. Last, we identified a small molecule compound that preferentially induces YTHDF2 degradation, which shows a potent antitumor effect alone but a better effect when combined with anti–PD-L1 or anti–PD-1 antibodies. Collectively, YTHDF2 appears to be a tumor-intrinsic regulator that orchestrates immune evasion, representing a promising target for enhancing cancer immunotherapy.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adl2171","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184478","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}
Munetomo Takahashi, Tsz Y. So, Vitalina Chamberlain-Evans, Robert Hughes, Juan Carlos Yam-Puc, Katarzyna Kania, Michelle Ruhle, Tiffeney Mann, Martijn J. Schuijs, Paul Coupland, Dean Naisbitt, Timotheus Y. F. Halim, Paul A. Lyons, Pietro Lio, Rahul Roychoudhuri, Klaus Okkenhaug, David J. Adams, Ken G. C. Smith, Duncan I. Jodrell, Michael A. Chapman, James E. D. Thaventhiran
{"title":"Intratumoral antigen signaling traps CD8+ T cells to confine exhaustion to the tumor site","authors":"Munetomo Takahashi, Tsz Y. So, Vitalina Chamberlain-Evans, Robert Hughes, Juan Carlos Yam-Puc, Katarzyna Kania, Michelle Ruhle, Tiffeney Mann, Martijn J. Schuijs, Paul Coupland, Dean Naisbitt, Timotheus Y. F. Halim, Paul A. Lyons, Pietro Lio, Rahul Roychoudhuri, Klaus Okkenhaug, David J. Adams, Ken G. C. Smith, Duncan I. Jodrell, Michael A. Chapman, James E. D. Thaventhiran","doi":"10.1126/sciimmunol.ade2094","DOIUrl":"10.1126/sciimmunol.ade2094","url":null,"abstract":"<div >Immunotherapy advances have been hindered by difficulties in tracking the behaviors of lymphocytes after antigen signaling. Here, we assessed the behavior of T cells active within tumors through the development of the antigen receptor signaling reporter (AgRSR) mouse, fate-mapping lymphocytes responding to antigens at specific times and locations. Contrary to reports describing the ready egress of T cells out of the tumor, we find that intratumoral antigen signaling traps CD8<sup>+</sup> T cells in the tumor. These clonal populations expand and become increasingly exhausted over time. By contrast, antigen-signaled regulatory T cell (T<sub>reg</sub>) clonal populations readily recirculate out of the tumor. Consequently, intratumoral antigen signaling acts as a gatekeeper to compartmentalize CD8<sup>+</sup> T cell responses, even within the same clonotype, thus enabling exhausted T cells to remain confined to a specific tumor tissue site.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093251","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}
{"title":"Heart failure promotes multimorbidity through innate immune memory","authors":"Yukiteru Nakayama, Katsuhito Fujiu, Tsukasa Oshima, Jun Matsuda, Junichi Sugita, Takumi James Matsubara, Yuxiang Liu, Kohsaku Goto, Kunihiro Kani, Ryoko Uchida, Norifumi Takeda, Hiroyuki Morita, Yingda Xiao, Michiko Hayashi, Yujin Maru, Eriko Hasumi, Toshiya Kojima, Soh Ishiguro, Yusuke Kijima, Nozomu Yachie, Satoshi Yamazaki, Ryo Yamamoto, Fujimi Kudo, Mio Nakanishi, Atsushi Iwama, Ryoji Fujiki, Atsushi Kaneda, Osamu Ohara, Ryozo Nagai, Ichiro Manabe, Issei Komuro","doi":"10.1126/sciimmunol.ade3814","DOIUrl":"10.1126/sciimmunol.ade3814","url":null,"abstract":"<div >Patients with heart failure (HF) often experience repeated acute decompensation and develop comorbidities such as chronic kidney disease and frailty syndrome. Although this suggests pathological interaction among comorbidities, the mechanisms linking them are poorly understood. Here, we identified alterations in hematopoietic stem cells (HSCs) as a critical driver of recurrent HF and associated comorbidities. Bone marrow transplantation from HF-experienced mice resulted in spontaneous cardiac dysfunction and fibrosis in recipient mice, as well as increased vulnerability to kidney and skeletal muscle insults. HF enhanced the capacity of HSCs to generate proinflammatory macrophages. In HF mice, global chromatin accessibility analysis and single-cell RNA-seq showed that transforming growth factor–β (TGF-β) signaling was suppressed in HSCs, which corresponded with repressed sympathetic nervous activity in bone marrow. Transplantation of bone marrow from mice in which TGF-β signaling was inhibited similarly exacerbated cardiac dysfunction. Collectively, these results suggest that cardiac stress modulates the epigenome of HSCs, which in turn alters their capacity to generate cardiac macrophage subpopulations. This change in HSCs may be a common driver of repeated HF events and comorbidity by serving as a key carrier of “stress memory.”</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.ade3814","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093294","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}
Rui Chen, Elena Lukianova, Ina Schim van der Loeff, Jarmila Stremenova Spegarova, Joseph D.P. Willet, Kieran D. James, Edward J. Ryder, Helen Griffin, Hanna IJspeert, Akshada Gajbhiye, Frederic Lamoliatte, Jose L. Marin-Rubio, Lisa Woodbine, Henrique Lemos, David J. Swan, Valeria Pintar, Kamal Sayes, Elias R. Ruiz-Morales, Simon Eastham, David Dixon, Martin Prete, Elena Prigmore, Penny Jeggo, Joan Boyes, Andrew Mellor, Lei Huang, Mirjam van der Burg, Karin R. Engelhardt, Asbjørg Stray-Pedersen, Hans Christian Erichsen, Andrew R. Gennery, Matthias Trost, David J. Adams, Graham Anderson, Anna Lorenc, Gosia Trynka, Sophie Hambleton
{"title":"NUDCD3 deficiency disrupts V(D)J recombination to cause SCID and Omenn syndrome","authors":"Rui Chen, Elena Lukianova, Ina Schim van der Loeff, Jarmila Stremenova Spegarova, Joseph D.P. Willet, Kieran D. James, Edward J. Ryder, Helen Griffin, Hanna IJspeert, Akshada Gajbhiye, Frederic Lamoliatte, Jose L. Marin-Rubio, Lisa Woodbine, Henrique Lemos, David J. Swan, Valeria Pintar, Kamal Sayes, Elias R. Ruiz-Morales, Simon Eastham, David Dixon, Martin Prete, Elena Prigmore, Penny Jeggo, Joan Boyes, Andrew Mellor, Lei Huang, Mirjam van der Burg, Karin R. Engelhardt, Asbjørg Stray-Pedersen, Hans Christian Erichsen, Andrew R. Gennery, Matthias Trost, David J. Adams, Graham Anderson, Anna Lorenc, Gosia Trynka, Sophie Hambleton","doi":"10.1126/sciimmunol.ade5705","DOIUrl":"10.1126/sciimmunol.ade5705","url":null,"abstract":"<div >Inborn errors of T cell development present a pediatric emergency in which timely curative therapy is informed by molecular diagnosis. In 11 affected patients across four consanguineous kindreds, we detected homozygosity for a single deleterious missense variant in the gene NudC domain–containing 3 (<i>NUDCD3</i>)<i>.</i> Two infants had severe combined immunodeficiency with the complete absence of T and B cells (T<sup> -</sup>B<sup>-</sup> SCID), whereas nine showed classical features of Omenn syndrome (OS). Restricted antigen receptor gene usage by residual T lymphocytes suggested impaired V(D)J recombination. Patient cells showed reduced expression of NUDCD3 protein and diminished ability to support RAG-mediated recombination in vitro, which was associated with pathologic sequestration of RAG1 in the nucleoli. Although impaired V(D)J recombination in a mouse model bearing the homologous variant led to milder immunologic abnormalities, NUDCD3 is absolutely required for healthy T and B cell development in humans.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.ade5705","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093322","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}
Blanda Di Luccia, Martina Molgora, Darya Khantakova, Natalia Jaeger, Hao-Wei Chang, Rafael S. Czepielewski, Beth A. Helmink, Emily J. Onufer, José L. Fachi, Bishan Bhattarai, Tihana Trsan, Patrick F. Rodrigues, JinChao Hou, Jennifer K. Bando, Cristiane Sécca da Silva, Marina Cella, Susan Gilfillan, Robert D. Schreiber, Jeffrey I. Gordon, Marco Colonna
{"title":"TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti–PD-1 tumor immunotherapy","authors":"Blanda Di Luccia, Martina Molgora, Darya Khantakova, Natalia Jaeger, Hao-Wei Chang, Rafael S. Czepielewski, Beth A. Helmink, Emily J. Onufer, José L. Fachi, Bishan Bhattarai, Tihana Trsan, Patrick F. Rodrigues, JinChao Hou, Jennifer K. Bando, Cristiane Sécca da Silva, Marina Cella, Susan Gilfillan, Robert D. Schreiber, Jeffrey I. Gordon, Marco Colonna","doi":"10.1126/sciimmunol.adi5374","DOIUrl":"10.1126/sciimmunol.adi5374","url":null,"abstract":"<div >The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti–programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti–PD-1. Here, we found that anti–PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of <i>Ruminococcus gnavus</i> in the gut microbiota. Gavage of wild-type mice with <i>R. gnavus</i> enhanced anti–PD-1–mediated tumor elimination, recapitulating the effect occurring in the absence of TREM2. A proinflammatory intestinal environment coincided with expansion, increased circulation, and migration of TNF-producing CD4<sup>+</sup> T cells to the tumor bed. Thus, TREM2 remotely controls anti–PD-1 immune checkpoint blockade through modulation of the intestinal immune environment and microbiota, with <i>R. gnavus</i> emerging as a potential probiotic agent for increasing responsiveness to anti-PD-1.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140953857","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}
Hieu Minh Ta, Dia Roy, Keman Zhang, Tyler Alban, Ivan Juric, Juan Dong, Prerana B. Parthasarathy, Sachin Patnaik, Elizabeth Delaney, Cassandra Gilmour, Amin Zakeri, Nidhi Shukla, Amit Rupani, Yee Peng Phoon, Caini Liu, Stefanie Avril, Brian Gastman, Timothy Chan, Li Lily Wang
{"title":"LRIG1 engages ligand VISTA and impairs tumor-specific CD8+ T cell responses","authors":"Hieu Minh Ta, Dia Roy, Keman Zhang, Tyler Alban, Ivan Juric, Juan Dong, Prerana B. Parthasarathy, Sachin Patnaik, Elizabeth Delaney, Cassandra Gilmour, Amin Zakeri, Nidhi Shukla, Amit Rupani, Yee Peng Phoon, Caini Liu, Stefanie Avril, Brian Gastman, Timothy Chan, Li Lily Wang","doi":"10.1126/sciimmunol.adi7418","DOIUrl":"10.1126/sciimmunol.adi7418","url":null,"abstract":"<div >Immune checkpoint blockade is a promising approach to activate antitumor immunity and improve the survival of patients with cancer. V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint target; however, the downstream signaling mechanisms are elusive. Here, we identify leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) as a VISTA binding partner, which acts as an inhibitory receptor by engaging VISTA and suppressing T cell receptor signaling pathways. Mice with T cell–specific LRIG1 deletion developed superior antitumor responses because of expansion of tumor-specific cytotoxic T lymphocytes (CTLs) with increased effector function and survival. Sustained tumor control was associated with a reduction of quiescent CTLs (TCF1<sup>+</sup> CD62L<sup>hi</sup> PD-1<sup>low</sup>) and a reciprocal increase in progenitor and memory-like CTLs (TCF1<sup>+</sup> PD-1<sup>+</sup>). In patients with melanoma, elevated LRIG1 expression on tumor-infiltrating CD8<sup>+</sup> CTLs correlated with resistance to immunotherapies. These results delineate the role of LRIG1 as an inhibitory immune checkpoint receptor and propose a rationale for targeting the VISTA/LRIG1 axis for cancer immunotherapy.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140953853","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}
Xuesong Wang, Christopher A. Cottrell, Xiaozhen Hu, Rashmi Ray, Maria Bottermann, Paula Maldonado Villavicencio, Yu Yan, Zhenfei Xie, John E. Warner, Jordan Renae Ellis-Pugh, Oleksandr Kalyuzhniy, Alessia Liguori, Jordan R. Willis, Sergey Menis, Sebastian Rämisch, Saman Eskandarzadeh, Michael Kubitz, Ryan Tingle, Nicole Phelps, Bettina Groschel, Sunny Himansu, Andrea Carfi, Kathrin H. Kirsch, Stephanie R. Weldon, Usha Nair, William R. Schief, Facundo D. Batista
{"title":"mRNA-LNP prime boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models","authors":"Xuesong Wang, Christopher A. Cottrell, Xiaozhen Hu, Rashmi Ray, Maria Bottermann, Paula Maldonado Villavicencio, Yu Yan, Zhenfei Xie, John E. Warner, Jordan Renae Ellis-Pugh, Oleksandr Kalyuzhniy, Alessia Liguori, Jordan R. Willis, Sergey Menis, Sebastian Rämisch, Saman Eskandarzadeh, Michael Kubitz, Ryan Tingle, Nicole Phelps, Bettina Groschel, Sunny Himansu, Andrea Carfi, Kathrin H. Kirsch, Stephanie R. Weldon, Usha Nair, William R. Schief, Facundo D. Batista","doi":"10.1126/sciimmunol.adn0622","DOIUrl":"10.1126/sciimmunol.adn0622","url":null,"abstract":"<div >Germline-targeting (GT) protein immunogens to induce VRC01-class broadly neutralizing antibodies (bnAbs) to the CD4-binding site of the HIV envelope (Env) have shown promise in clinical trials. Here, we preclinically validated a lipid nanoparticle–encapsulated nucleoside mRNA (mRNA-LNP) encoding eOD-GT8 60mer as a soluble self-assembling nanoparticle in mouse models. In a model with three humanized B cell lineages bearing distinct VRC01-precursor B cell receptors (BCRs) with similar affinities for eOD-GT8, all lineages could be simultaneously primed and undergo diversification and affinity maturation without exclusionary competition. Boosts drove precursor B cell participation in germinal centers; the accumulation of somatic hypermutations, including in key VRC01-class positions; and affinity maturation to boost and native-like antigens in two of the three precursor lineages. We have preclinically validated a prime-boost regimen of soluble self-assembling nanoparticles encoded by mRNA-LNP, demonstrating that multiple lineages can be primed, boosted, and diversified along the bnAb pathway.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adn0622","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140953313","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}
Alessandro Vacchini, Andrew Chancellor, Qinmei Yang, Rodrigo Colombo, Julian Spagnuolo, Giuliano Berloffa, Daniel Joss, Ove Øyås, Chiara Lecchi, Giulia De Simone, Aisha Beshirova, Vladimir Nosi, José Pedro Loureiro, Aurelia Morabito, Corinne De Gregorio, Michael Pfeffer, Verena Schaefer, Gennaro Prota, Alfred Zippelius, Jörg Stelling, Daniel Häussinger, Laura Brunelli, Peter Villalta, Marco Lepore, Enrico Davoli, Silvia Balbo, Lucia Mori, Gennaro De Libero
{"title":"Nucleobase adducts bind MR1 and stimulate MR1-restricted T cells","authors":"Alessandro Vacchini, Andrew Chancellor, Qinmei Yang, Rodrigo Colombo, Julian Spagnuolo, Giuliano Berloffa, Daniel Joss, Ove Øyås, Chiara Lecchi, Giulia De Simone, Aisha Beshirova, Vladimir Nosi, José Pedro Loureiro, Aurelia Morabito, Corinne De Gregorio, Michael Pfeffer, Verena Schaefer, Gennaro Prota, Alfred Zippelius, Jörg Stelling, Daniel Häussinger, Laura Brunelli, Peter Villalta, Marco Lepore, Enrico Davoli, Silvia Balbo, Lucia Mori, Gennaro De Libero","doi":"10.1126/sciimmunol.adn0126","DOIUrl":"10.1126/sciimmunol.adn0126","url":null,"abstract":"<div >MR1T cells are a recently found class of T cells that recognize antigens presented by the major histocompatibility complex-I–related molecule MR1 in the absence of microbial infection. The nature of the self-antigens that stimulate MR1T cells remains unclear, hampering our understanding of their physiological role and therapeutic potential. By combining genetic, pharmacological, and biochemical approaches, we found that carbonyl stress and changes in nucleobase metabolism in target cells promote MR1T cell activation. Stimulatory compounds formed by carbonyl adducts of nucleobases were detected within MR1 molecules produced by tumor cells, and their abundance and antigenicity were enhanced by drugs that induce carbonyl accumulation. Our data reveal carbonyl-nucleobase adducts as MR1T cell antigens. Recognizing cells under carbonyl stress allows MR1T cells to monitor cellular metabolic changes with physiological and therapeutic implications.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905011","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}
{"title":"Erratum for the Research Article “Transcriptomes and metabolism define mouse and human MAIT cell populations” by S. Chandra et al.","authors":"","doi":"10.1126/sciimmunol.adp9609","DOIUrl":"10.1126/sciimmunol.adp9609","url":null,"abstract":"","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905008","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}
Chuan Qin, Min Zhang, Da-Peng Mou, Luo-Qi Zhou, Ming-Hao Dong, Liang Huang, Wen Wang, Song-Bai Cai, Yun-Fan You, Ke Shang, Jun Xiao, Di Wang, Chun-Rui Li, Yi Hao, Michael Heming, Long-Jun Wu, Gerd Meyer Zu Hörste, Chen Dong, Bi-Tao Bu, Dai-Shi Tian, Wei Wang
{"title":"Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity","authors":"Chuan Qin, Min Zhang, Da-Peng Mou, Luo-Qi Zhou, Ming-Hao Dong, Liang Huang, Wen Wang, Song-Bai Cai, Yun-Fan You, Ke Shang, Jun Xiao, Di Wang, Chun-Rui Li, Yi Hao, Michael Heming, Long-Jun Wu, Gerd Meyer Zu Hörste, Chen Dong, Bi-Tao Bu, Dai-Shi Tian, Wei Wang","doi":"10.1126/sciimmunol.adj9730","DOIUrl":"10.1126/sciimmunol.adj9730","url":null,"abstract":"<div >Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti–B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8<sup>+</sup> CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adj9730","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905013","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}
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