Nature Immunology最新文献_第10页

Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity 肿瘤微环境中的氯化钠可增强 T 细胞的代谢能力和细胞毒性

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-28 DOI: 10.1038/s41590-024-01918-6

Dominik Soll, Chang-Feng Chu, Shan Sun, Veronika Lutz, Mahima Arunkumar, Mariam Gachechiladze, Sascha Schäuble, Maha Alissa-Alkhalaf, Trang Nguyen, Michelle-Amirah Khalil, Ignacio Garcia-Ribelles, Michael Mueller, Katrin Buder, Bernhard Michalke, Gianni Panagiotou, Kai Ziegler-Martin, Pascal Benz, Philipp Schatzlmaier, Karsten Hiller, Hannes Stockinger, Maik Luu, Kilian Schober, Carolin Moosmann, Wolfgang W. Schamel, Magdalena Huber, Christina E. Zielinski

{"title":"Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity","authors":"Dominik Soll, Chang-Feng Chu, Shan Sun, Veronika Lutz, Mahima Arunkumar, Mariam Gachechiladze, Sascha Schäuble, Maha Alissa-Alkhalaf, Trang Nguyen, Michelle-Amirah Khalil, Ignacio Garcia-Ribelles, Michael Mueller, Katrin Buder, Bernhard Michalke, Gianni Panagiotou, Kai Ziegler-Martin, Pascal Benz, Philipp Schatzlmaier, Karsten Hiller, Hannes Stockinger, Maik Luu, Kilian Schober, Carolin Moosmann, Wolfgang W. Schamel, Magdalena Huber, Christina E. Zielinski","doi":"10.1038/s41590-024-01918-6","DOIUrl":"10.1038/s41590-024-01918-6","url":null,"abstract":"The efficacy of antitumor immunity is associated with the metabolic state of cytotoxic T cells, which is sensitive to the tumor microenvironment. Whether ionic signals affect adaptive antitumor immune responses is unclear. In the present study, we show that there is an enrichment of sodium in solid tumors from patients with breast cancer. Sodium chloride (NaCl) enhances the activation state and effector functions of human CD8+ T cells, which is associated with enhanced metabolic fitness. These NaCl-induced effects translate into increased tumor cell killing in vitro and in vivo. Mechanistically, NaCl-induced changes in CD8+ T cells are linked to sodium-induced upregulation of Na+/K+-ATPase activity, followed by membrane hyperpolarization, which magnifies the electromotive force for T cell receptor (TCR)-induced calcium influx and downstream TCR signaling. We therefore propose that NaCl is a positive regulator of acute antitumor immunity that might be modulated for ex vivo conditioning of therapeutic T cells, such as CAR T cells. In this paper and the related paper from Lugli and colleagues the authors show that high levels of NaCl inside the tumor have a beneficial effect on CD8+ T cells and their ability to control tumor growth as a result of enhanced T cell receptor activity.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 10","pages":"1830-1844"},"PeriodicalIF":27.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01918-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142084850","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

The hidden strength of CD8+ T cells in chronic hepatitis B 慢性乙型肝炎 CD8+ T 细胞的隐性优势

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-28 DOI: 10.1038/s41590-024-01939-1

Francesco Andreata, Matteo Iannacone

引用次数: 0

Attenuated effector T cells are linked to control of chronic HBV infection 减弱的效应 T 细胞与控制慢性 HBV 感染有关

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-28 DOI: 10.1038/s41590-024-01928-4

Kathrin Heim, Sagar, Özlem Sogukpinar, Sian Llewellyn-Lacey, David A. Price, Florian Emmerich, Anke R. M. Kraft, Markus Cornberg, Sophie Kielbassa, Percy Knolle, Dirk Wohlleber, Bertram Bengsch, Tobias Boettler, Christoph Neumann-Haefelin, Robert Thimme, Maike Hofmann

{"title":"Attenuated effector T cells are linked to control of chronic HBV infection","authors":"Kathrin Heim,  Sagar, Özlem Sogukpinar, Sian Llewellyn-Lacey, David A. Price, Florian Emmerich, Anke R. M. Kraft, Markus Cornberg, Sophie Kielbassa, Percy Knolle, Dirk Wohlleber, Bertram Bengsch, Tobias Boettler, Christoph Neumann-Haefelin, Robert Thimme, Maike Hofmann","doi":"10.1038/s41590-024-01928-4","DOIUrl":"10.1038/s41590-024-01928-4","url":null,"abstract":"Hepatitis B virus (HBV)-specific CD8+ T cells play a dominant role during acute-resolving HBV infection but are functionally impaired during chronic HBV infection in humans. These functional deficits have been linked with metabolic and phenotypic heterogeneity, but it has remained unclear to what extent different subsets of HBV-specific CD8+ T cells still suppress viral replication. We addressed this issue by deep profiling, functional testing and perturbation of HBV-specific CD8+ T cells during different phases of chronic HBV infection. Our data revealed a mechanism of effector CD8+ T cell attenuation that emerges alongside classical CD8+ T cell exhaustion. Attenuated HBV-specific CD8+ T cells were characterized by cytotoxic properties and a dampened effector differentiation program, determined by antigen recognition and TGFβ signaling, and were associated with viral control during chronic HBV infection. These observations identify a distinct subset of CD8+ T cells linked with immune efficacy in the context of a chronic human viral infection with immunotherapeutic potential. Heim et al. investigate the role of CD8+ T cells specific to HBV polymerase in the context of chronic HBV infection. They identify a unique subset of CD8+ T cells with an attenuated effector function. The attenuation is driven by TGFβ signaling, offering new insights into the immune landscape of chronic HBV infection and suggesting potential therapeutic avenues for modulating these cells to enhance viral control.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 9","pages":"1650-1662"},"PeriodicalIF":27.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01928-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142084852","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

A mass cytometry method pairing T cell receptor and differentiation state analysis 将 T 细胞受体与分化状态分析相结合的质谱法。

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-27 DOI: 10.1038/s41590-024-01937-3

Jesse Garcia Castillo, Rachel DeBarge, Abigail Mende, Iliana Tenvooren, Diana M. Marquez, Adrian Straub, Dirk H. Busch, Matthew H. Spitzer, Michel DuPage

{"title":"A mass cytometry method pairing T cell receptor and differentiation state analysis","authors":"Jesse Garcia Castillo, Rachel DeBarge, Abigail Mende, Iliana Tenvooren, Diana M. Marquez, Adrian Straub, Dirk H. Busch, Matthew H. Spitzer, Michel DuPage","doi":"10.1038/s41590-024-01937-3","DOIUrl":"10.1038/s41590-024-01937-3","url":null,"abstract":"T cell antigen receptor (TCR) recognition followed by clonal expansion is a fundamental feature of adaptive immune responses. Here, we present a mass cytometric (CyTOF) approach to track T cell responses by combining antibodies for specific TCR Vα and Vβ chains with antibodies against T cell activation and differentiation proteins in mice. This strategy identifies expansions of CD8+ and CD4+ T cells expressing specific Vβ and Vα chains with varying differentiation states in response to Listeria monocytogenes, tumors and respiratory influenza infection. Expanded T cell populations expressing Vβ chains could be directly linked to the recognition of specific antigens from Listeria, tumor cells or influenza. In the setting of influenza infection, we found that common therapeutic approaches of intramuscular vaccination or convalescent serum transfer altered the TCR diversity and differentiation state of responding T cells. Thus, we present a method to monitor broad changes in TCR use paired with T cell phenotyping during adaptive immune responses. Here the authors present a mass cytometry-based method for identification of antigen-specific T cells and their differentiation state, testing it in cancer, bacterial and viral mouse models.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 9","pages":"1754-1763"},"PeriodicalIF":27.7,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081015","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

Long-term antiretroviral therapy rejuvenates the HIV-specific CD8+ T cell response 长期抗逆转录病毒疗法使艾滋病毒特异性 CD8+ T 细胞反应恢复活力

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-23 DOI: 10.1038/s41590-024-01924-8

Joel N. Blankson

引用次数: 0

Clonal succession after prolonged antiretroviral therapy rejuvenates CD8+ T cell responses against HIV-1 长期抗逆转录病毒疗法后的克隆继承可使 CD8+ T 细胞对 HIV-1 的反应恢复活力

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-23 DOI: 10.1038/s41590-024-01931-9

Eoghann White, Laura Papagno, Assia Samri, Kenji Sugata, Boris Hejblum, Amy R. Henry, Daniel C. Rogan, Samuel Darko, Patricia Recordon-Pinson, Yasmine Dudoit, Sian Llewellyn-Lacey, Lisa A. Chakrabarti, Florence Buseyne, Stephen A. Migueles, David A. Price, Marie-Aline Andreola, Yorifumi Satou, Rodolphe Thiebaut, Christine Katlama, Brigitte Autran, Daniel C. Douek, Victor Appay

{"title":"Clonal succession after prolonged antiretroviral therapy rejuvenates CD8+ T cell responses against HIV-1","authors":"Eoghann White, Laura Papagno, Assia Samri, Kenji Sugata, Boris Hejblum, Amy R. Henry, Daniel C. Rogan, Samuel Darko, Patricia Recordon-Pinson, Yasmine Dudoit, Sian Llewellyn-Lacey, Lisa A. Chakrabarti, Florence Buseyne, Stephen A. Migueles, David A. Price, Marie-Aline Andreola, Yorifumi Satou, Rodolphe Thiebaut, Christine Katlama, Brigitte Autran, Daniel C. Douek, Victor Appay","doi":"10.1038/s41590-024-01931-9","DOIUrl":"10.1038/s41590-024-01931-9","url":null,"abstract":"Human immunodeficiency virus 1 (HIV-1) infection is characterized by a dynamic and persistent state of viral replication that overwhelms the host immune system in the absence of antiretroviral therapy (ART). The impact of prolonged treatment on the antiviral efficacy of HIV-1-specific CD8+ T cells has nonetheless remained unknown. Here, we used single-cell technologies to address this issue in a cohort of aging individuals infected early during the pandemic and subsequently treated with continuous ART. Our data showed that long-term ART was associated with a process of clonal succession, which effectively rejuvenated HIV-1-specific CD8+ T cell populations in the face of immune senescence. Tracking individual transcriptomes further revealed that initially dominant CD8+ T cell clonotypes displayed signatures of exhaustion and terminal differentiation, whereas newly dominant CD8+ T cell clonotypes displayed signatures of early differentiation and stemness associated with natural control of viral replication. These findings reveal a degree of immune resilience that could inform adjunctive treatments for HIV-1. Appay and colleagues show that long-term antiretroviral therapy is associated with clonal succession of HIV-1-specific CD8+ T cell populations, which evolved from an exhaustion-like toward a stemness-like phenotype.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 9","pages":"1555-1564"},"PeriodicalIF":27.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042701","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

Mapping spatial organization and genetic cell-state regulators to target immune evasion in ovarian cancer 绘制空间组织和遗传细胞状态调节因子图，以卵巢癌中的免疫逃避为目标

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-23 DOI: 10.1038/s41590-024-01943-5

Christine Yiwen Yeh, Karmen Aguirre, Olivia Laveroni, Subin Kim, Aihui Wang, Brooke Liang, Xiaoming Zhang, Lucy M. Han, Raeline Valbuena, Michael C. Bassik, Young-Min Kim, Sylvia K. Plevritis, Michael P. Snyder, Brooke E. Howitt, Livnat Jerby

{"title":"Mapping spatial organization and genetic cell-state regulators to target immune evasion in ovarian cancer","authors":"Christine Yiwen Yeh, Karmen Aguirre, Olivia Laveroni, Subin Kim, Aihui Wang, Brooke Liang, Xiaoming Zhang, Lucy M. Han, Raeline Valbuena, Michael C. Bassik, Young-Min Kim, Sylvia K. Plevritis, Michael P. Snyder, Brooke E. Howitt, Livnat Jerby","doi":"10.1038/s41590-024-01943-5","DOIUrl":"10.1038/s41590-024-01943-5","url":null,"abstract":"The drivers of immune evasion are not entirely clear, limiting the success of cancer immunotherapies. Here we applied single-cell spatial and perturbational transcriptomics to delineate immune evasion in high-grade serous tubo-ovarian cancer. To this end, we first mapped the spatial organization of high-grade serous tubo-ovarian cancer by profiling more than 2.5 million cells in situ in 130 tumors from 94 patients. This revealed a malignant cell state that reflects tumor genetics and is predictive of T cell and natural killer cell infiltration levels and response to immune checkpoint blockade. We then performed Perturb-seq screens and identified genetic perturbations—including knockout of PTPN1 and ACTR8—that trigger this malignant cell state. Finally, we show that these perturbations, as well as a PTPN1/PTPN2 inhibitor, sensitize ovarian cancer cells to T cell and natural killer cell cytotoxicity, as predicted. This study thus identifies ways to study and target immune evasion by linking genetic variation, cell-state regulators and spatial biology. Here the authors provide a resource for ovarian cancer combining spatial transcriptomics, genomics, CRISPR Perturb-seq screens and in silico methods to focus on T cells and natural killer cells in the tumor and their role in immune evasion.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 10","pages":"1943-1958"},"PeriodicalIF":27.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01943-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042702","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

Transcriptional function of E2A, Ebf1, Pax5, Ikaros and Aiolos analyzed by in vivo acute protein degradation in early B cell development 通过体内急性蛋白降解分析早期 B 细胞发育过程中 E2A、Ebf1、Pax5、Ikaros 和 Aiolos 的转录功能

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-23 DOI: 10.1038/s41590-024-01933-7

Anna S. Fedl, Hiromi Tagoh, Sarah Gruenbacher, Qiong Sun, Robyn L. Schenk, Kimon Froussios, Markus Jaritz, Meinrad Busslinger, Tanja A. Schwickert

{"title":"Transcriptional function of E2A, Ebf1, Pax5, Ikaros and Aiolos analyzed by in vivo acute protein degradation in early B cell development","authors":"Anna S. Fedl, Hiromi Tagoh, Sarah Gruenbacher, Qiong Sun, Robyn L. Schenk, Kimon Froussios, Markus Jaritz, Meinrad Busslinger, Tanja A. Schwickert","doi":"10.1038/s41590-024-01933-7","DOIUrl":"10.1038/s41590-024-01933-7","url":null,"abstract":"Early B cell lymphopoiesis depends on E2A, Ebf1, Pax5 and Ikaros family members. In the present study, we used acute protein degradation in mice to identify direct target genes of these transcription factors in pro-B, small pre-B and immature B cells. E2A, Ebf1 and Pax5 predominantly function as transcriptional activators by inducing open chromatin at their target genes, have largely unique functions and are essential for early B cell maintenance. Ikaros and Aiolos act as dedicated repressors to cooperatively control early B cell development. The surrogate light-chain genes Igll1 and Vpreb1 are directly activated by Ebf1 and Pax5 in pro-B cells and directly repressed by Ikaros and Aiolos in small pre-B cells. Pax5 and E2A contribute to V(D)J recombination by activating Rag1, Rag2, Dntt, Irf4 and Irf8. Similar to Pax5, Ebf1 also represses the cohesin-release factor gene Wapl to mediate prolonged loop extrusion across the Igh locus. In summary, in vivo protein degradation has provided unprecedented insight into the control of early B cell lymphopoiesis by five transcription factors. By use of a degron-mediated acute protein degradation model, Schwickert and colleagues are able to distinguish between direct and indirect gene targets of multiple transcription factors involved in early B cell development.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 9","pages":"1663-1677"},"PeriodicalIF":27.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042703","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

Mechanism for controlled assembly of transcriptional condensates by Aire 艾尔转录凝聚体的受控组装机制

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-21 DOI: 10.1038/s41590-024-01922-w

Yu-San Huoh, Qianxia Zhang, Ricarda Törner, Sylvan C. Baca, Haribabu Arthanari, Sun Hur

{"title":"Mechanism for controlled assembly of transcriptional condensates by Aire","authors":"Yu-San Huoh, Qianxia Zhang, Ricarda Törner, Sylvan C. Baca, Haribabu Arthanari, Sun Hur","doi":"10.1038/s41590-024-01922-w","DOIUrl":"10.1038/s41590-024-01922-w","url":null,"abstract":"Transcriptional condensates play a crucial role in gene expression and regulation, yet their assembly mechanisms remain poorly understood. Here, we report a multi-layered mechanism for condensate assembly by autoimmune regulator (Aire), an essential transcriptional regulator that orchestrates gene expression reprogramming for central T cell tolerance. Aire condensates assemble on enhancers, stimulating local transcriptional activities and connecting disparate inter-chromosomal loci. This functional condensate formation hinges upon the coordination between three Aire domains: polymerization domain caspase activation recruitment domain (CARD), histone-binding domain (first plant homeodomain (PHD1)), and C-terminal tail (CTT). Specifically, CTT binds coactivators CBP/p300, recruiting Aire to CBP/p300-rich enhancers and promoting CARD-mediated condensate assembly. Conversely, PHD1 binds to the ubiquitous histone mark H3K4me0, keeping Aire dispersed throughout the genome until Aire nucleates on enhancers. Our findings showed that the balance between PHD1-mediated suppression and CTT-mediated stimulation of Aire polymerization is crucial to form transcriptionally active condensates at target sites, providing new insights into controlled polymerization of transcriptional regulators. Sun Hur and colleagues examine the mechanism of Aire protein function underlying peripheral tissue antigen gene expression in thymic mTECs. They show that Aire condensates assemble on enhancers that are subject to intricate regulatory mechanisms, ensuring tight coordination of Aire CARD polymerization with genomic target recognition.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 9","pages":"1580-1592"},"PeriodicalIF":27.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01922-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013805","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

Tumor editing suppresses innate and adaptive antitumor immunity and is reversed by inhibiting DNA methylation 肿瘤编辑会抑制先天性和适应性抗肿瘤免疫，而抑制 DNA 甲基化则可逆转这种情况

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-08-21 DOI: 10.1038/s41590-024-01932-8

Ying Zhang, Pourya Naderi Yeganeh, Haiwei Zhang, Simon Yuan Wang, Zhouyihan Li, Bowen Gu, Dian-Jang Lee, Zhibin Zhang, Athanasios Ploumakis, Ming Shi, Hao Wu, Eric Lieberman Greer, Winston Hide, Judy Lieberman

{"title":"Tumor editing suppresses innate and adaptive antitumor immunity and is reversed by inhibiting DNA methylation","authors":"Ying Zhang, Pourya Naderi Yeganeh, Haiwei Zhang, Simon Yuan Wang, Zhouyihan Li, Bowen Gu, Dian-Jang Lee, Zhibin Zhang, Athanasios Ploumakis, Ming Shi, Hao Wu, Eric Lieberman Greer, Winston Hide, Judy Lieberman","doi":"10.1038/s41590-024-01932-8","DOIUrl":"10.1038/s41590-024-01932-8","url":null,"abstract":"Cancer cells edit gene expression to evade immunosurveillance. However, genome-wide studies of gene editing during early tumorigenesis are lacking. Here we used single-cell RNA sequencing in a breast cancer genetically engineered mouse model (GEMM) to identify edited genes without bias. Late tumors repressed antitumor immunity genes, reducing infiltrating immune cells and tumor–immune cell communications. Innate immune genes, especially interferon-stimulated genes, dominated the list of downregulated tumor genes, while genes that regulate cell-intrinsic malignancy were mostly unedited. Naive and activated CD8+ T cells in early tumors were replaced with exhausted or precursor-exhausted cells in late tumors. Repression of immune genes was reversed by inhibiting DNA methylation using low-dose decitabine, which suppressed tumor growth and restored immune control, increasing the number, functionality and memory of tumor-infiltrating lymphocytes and reducing the number of myeloid suppressor cells. Decitabine induced important interferon, pyroptosis and necroptosis genes, inflammatory cell death and immune control in GEMM and implanted breast and melanoma tumors. Tumor immunoediting occurs early during tumorigenesis and is thereby difficult to study. Here the authors overcome this issue using an aggressive breast cancer model that enables them to compare and contrast the trancriptomic state of early versus late tumors.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 10","pages":"1858-1870"},"PeriodicalIF":27.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013856","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