Cellular &Molecular Immunology最新文献

{"title":"NRP1 instructs IL-17-producing ILC3s to drive colitis progression","authors":"Ying Wang, Jianye Wang, Gaoyu Liu, Xianfu Yi, Jingyi Wu, Hailong Cao, Lijuan Zhang, Pan Zhou, Yong Fan, Ying Yu, Qiang Liu, Zhi Yao, Haitao Wang, Jie Zhou","doi":"10.1038/s41423-024-01246-7","DOIUrl":"10.1038/s41423-024-01246-7","url":null,"abstract":"Group 3 innate lymphoid cells (ILC3s) control tissue homeostasis and orchestrate mucosal inflammation; however, the precise mechanisms governing ILC3 activity are fully understood. Here, we identified the transmembrane protein neuropilin-1 (NRP1) as a positive regulator of interleukin (IL)-17-producing ILC3s in the intestine. NRP1 was markedly upregulated in intestinal mucosal biopsies from patients with inflammatory bowel disease (IBD) compared with healthy controls. Genetic deficiency of NRP1 reduces the frequency of ILC3s in the gut and impairs their production of IL-17A in an NF-κB signaling-dependent and cell-intrinsic manner. The diminished IL-17A production in ILC3s altered the composition of the microbiota and improved the outcome of dextran sodium sulfate (DSS)-induced colitis. Furthermore, pharmacological inhibition of NRP1 with EG00229 alleviated the severity of colitis. These observations demonstrated the critical role of NRP1 in the control of intestinal ILC3s, suggesting that NRP1 is a potential therapeutic target for IBD.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 2","pages":"161-175"},"PeriodicalIF":21.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909159","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":"Sequential STING and CD40 agonism drives massive expansion of tumor-specific T cells in liposomal peptide vaccines","authors":"Dmitrij Ostroumov, Naomi Benne, Fernando Lozano Vigario, Oscar Escalona-Rayo, Ksenia Dodz, Sarah Sauer, Lena Luisa Suhl, Hans Heiner Wedemeyer, Florian Kühnel, Bram Slütter, Thomas Christian Wirth","doi":"10.1038/s41423-024-01249-4","DOIUrl":"10.1038/s41423-024-01249-4","url":null,"abstract":"The clinical use of cancer vaccines is hampered by the low magnitude of induced T-cell responses and the need for repetitive antigen stimulation. Here, we demonstrate that liposomal formulations with incorporated STING agonists are optimally suited to deliver peptide antigens to dendritic cells in vivo and to activate dendritic cells in secondary lymphoid organs. One week after liposomal priming, systemic administration of peptides and a costimulatory agonistic CD40 antibody enables ultrarapid expansion of T cells, resulting in massive expansion of tumor-specific T cells in the peripheral blood two weeks after priming. In the MC-38 colon cancer model, this synthetic prime-boost regimen induces rapid regression and cure of large established subcutaneous cancers via the use of a single tumor-specific neoantigen. These experiments demonstrate the feasibility of liposome-based heterologous vaccination regimens to increase the therapeutic efficacy of peptide vaccines in the context of immunogenic adjuvants and costimulatory booster immunizations. Our results provide a rationale for the further development of modern liposomal peptide vaccines for cancer therapy.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 2","pages":"150-160"},"PeriodicalIF":21.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909161","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}

{"title":"A special RELationship between sugar and tumor-infiltrating regulatory T cells","authors":"Ingo Schmitz","doi":"10.1038/s41423-024-01248-5","DOIUrl":"10.1038/s41423-024-01248-5","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 3","pages":"330-332"},"PeriodicalIF":21.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01248-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834335","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}

{"title":"Effective immunosurveillance of clonally expanded mammary aneuploid cells","authors":"Lorenzo Galluzzi, Gwenola Manic, Ilio Vitale","doi":"10.1038/s41423-024-01250-x","DOIUrl":"10.1038/s41423-024-01250-x","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 2","pages":"131-133"},"PeriodicalIF":21.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817418","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":"MYO1F regulates T-cell activation and glycolytic metabolism by promoting the acetylation of GAPDH","authors":"Zhihui Cui, Heping Wang, Xiong Feng, Chuyu Wu, Ming Yi, Ruirui He, Ting Pan, Ru Gao, Lingyun Feng, Bo Zeng, Guoling Huang, Yuan Wang, Yanyun Du, Cun-jin Zhang, Xue Xiao, Chenhui Wang","doi":"10.1038/s41423-024-01247-6","DOIUrl":"10.1038/s41423-024-01247-6","url":null,"abstract":"Proper cellular metabolism in T cells is critical for a productive immune response. However, when dysregulated by intrinsic or extrinsic metabolic factors, T cells may contribute to a wide spectrum of diseases, such as cancers and autoimmune diseases. However, the metabolic regulation of T cells remains incompletely understood. Here, we show that MYO1F is required for human and mouse T-cell activation after TCR stimulation and that T-cell-specific Myo1f knockout mice exhibit an increased tumor burden and attenuated EAE severity due to impaired T-cell activation in vivo. Mechanistically, after TCR stimulation, MYO1F is phosphorylated by LCK at tyrosines 607 and 634, which is critical for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) acetylation at Lys84, 86 and 227 mediated by α-TAT1, which is an acetyltransferase, and these processes are important for its activation, cellular glycolysis and thus the effector function of T cells. Importantly, we show that a fusion protein of VAV1-MYO1F, a recurrent peripheral T-cell lymphoma (PTCL)-associated oncogenic protein, promotes hyperacetylation of GAPDH and its activation, which leads to aberrant glycolysis and T-cell proliferation, and that inhibition of the activity of GAPDH significantly limits T-cell activation and proliferation and extends the survival of hVAV1-MYO1F knock-in mice. Moreover, hyperacetylation of GAPDH was confirmed in human PTCL patient samples containing the VAV1-MYO1F gene fusion. Overall, this study revealed not only the mechanisms by which MYO1F regulates T-cell metabolism and VAV1-MYO1F fusion-induced PTCL but also promising therapeutic targets for the treatment of PTCL.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 2","pages":"176-190"},"PeriodicalIF":21.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817420","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":"Immunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors","authors":"Elena Catanzaro, Manuel Beltrán-Visiedo, Lorenzo Galluzzi, Dmitri V. Krysko","doi":"10.1038/s41423-024-01245-8","DOIUrl":"10.1038/s41423-024-01245-8","url":null,"abstract":"While immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the clinical management of various malignancies, a large fraction of patients are refractory to ICIs employed as standalone therapeutics, necessitating the development of combinatorial treatment strategies. Immunogenic cell death (ICD) inducers have attracted considerable interest as combinatorial partners for ICIs, at least in part owing to their ability to initiate a tumor-targeting adaptive immune response. However, compared with either approach alone, combinatorial regimens involving ICD inducers and ICIs have not always shown superior clinical activity. Here, we discuss accumulating evidence on the therapeutic interactions between ICD inducers and immunotherapy with ICIs in oncological settings, identify key factors that may explain discrepancies between preclinical and clinical findings, and propose strategies that address existing challenges to increase the efficacy of these combinations in patients with cancer.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 1","pages":"24-39"},"PeriodicalIF":21.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01245-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799548","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}

{"title":"The antitumor activity of TGFβ-specific T cells is dependent on IL-6 signaling","authors":"Maria Perez-Penco, Mikkel Byrdal, Lucia Lara de la Torre, Marta Ballester, Shawez Khan, Majken Siersbæk, Inés Lecoq, Cecilie Oelvang Madsen, Julie Westerlin Kjeldsen, Inge Marie Svane, Morten Hansen, Marco Donia, Julia Sidenius Johansen, Lars Rønn Olsen, Lars Grøntved, Inna Markovna Chen, Luis Arnes, Morten Orebo Holmström, Mads Hald Andersen","doi":"10.1038/s41423-024-01238-7","DOIUrl":"10.1038/s41423-024-01238-7","url":null,"abstract":"Although interleukin (IL)-6 is considered immunosuppressive and tumor-promoting, emerging evidence suggests that it may support antitumor immunity. While combining immune checkpoint inhibitors (ICIs) and radiotherapy in patients with pancreatic cancer (PC) has yielded promising clinical results, the addition of an anti-IL-6 receptor (IL-6R) antibody has failed to elicit clinical benefits. Notably, a robust TGFβ-specific immune response at baseline in PC patients treated solely with ICIs and radiotherapy correlated with improved survival. Recent preclinical studies demonstrated the efficacy of a TGFβ-based immune modulatory vaccine in controlling PC tumor growth, underscoring the important role of TGFβ-specific immunity in PC. Here, we explored the importance of IL-6 for TGFβ-specific immunity in PC. In a murine model of PC, coadministration of the TGFβ-based immune modulatory vaccine with an anti-IL-6R antibody rendered the vaccine ineffective. IL-6R blockade hampered the development of vaccine-induced T-cells and tumoral T-cell infiltration. Furthermore, it impaired the myeloid population, resulting in increased tumor-associated macrophage infiltration and an enhanced immunosuppressive phenotype. In PC patients, in contrast to those receiving only ICIs and radiotherapy, robust TGFβ-specific T-cell responses at baseline did not correlate with improved survival in patients receiving ICIs, radiotherapy and IL-6R blockade. Peripheral blood immunophenotyping revealed that IL-6R blockade altered the T-cell and monocytic compartments, which was consistent with the findings in the murine model. Our data suggest that the antitumor efficacy of TGFβ-specific T cells in PC depends on the presence of IL-6 within the tumor. Consequently, caution should be exercised when employing IL-6R blockade in patients receiving cancer immunotherapy.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 1","pages":"111-126"},"PeriodicalIF":21.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01238-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799561","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}

{"title":"Neutrophils in cancer: from biology to therapy","authors":"Leo Koenderman, Nienke Vrisekoop","doi":"10.1038/s41423-024-01244-9","DOIUrl":"10.1038/s41423-024-01244-9","url":null,"abstract":"The view of neutrophils has shifted from simple phagocytic cells, whose main function is to kill pathogens, to very complex cells that are also involved in immune regulation and tissue repair. These cells are essential for maintaining and regaining tissue homeostasis. Neutrophils can be viewed as double-edged swords in a range of situations. The potent killing machinery necessary for immune responses to pathogens can easily lead to collateral damage to host tissues when inappropriately controlled. Furthermore, some subtypes of neutrophils are potent pathogen killers, whereas others are immunosuppressive or can aid in tissue healing. Finally, in tumor immunology, many examples of both protumorigenic and antitumorigenic properties of neutrophils have been described. This has important consequences for cancer therapy, as targeting neutrophils can lead to either suppressed or stimulated antitumor responses. This review will discuss the current knowledge regarding the pro- and antitumorigenic roles of neutrophils, leading to the concept of a confused state of neutrophil-driven pro-/antitumor responses.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 1","pages":"4-23"},"PeriodicalIF":21.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01244-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799551","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}

{"title":"Esophageal ILC2s mediate abnormal epithelial remodeling in eosinophilic esophagitis via Areg-EGFR signaling","authors":"MinYeong Lim, Taesoo Kim, Hyesung Kim, Bo Gun Jang, Jae Kyung Myung, Hye Young Kim","doi":"10.1038/s41423-024-01242-x","DOIUrl":"10.1038/s41423-024-01242-x","url":null,"abstract":"Eosinophilic esophagitis (EoE) is a chronic allergic disorder characterized by eosinophilia and epithelial thickening, resulting in dysphagia. While emerging evidence implicates increased frequencies of group 2 innate lymphoid cells (ILC2s) and increased interleukin (IL)-33 expression in EoE pathogenesis, the precise mechanisms remain unclear. In this study, we investigated the role of ILC2s in EoE pathogenesis. We observed an abundance of KLRG1+ ILC2s in the esophagi of healthy mice, with their numbers significantly increasing in murine EoE models and humans. Using a murine EoE model, we demonstrated the recapitulation of EoE-associated features, including basal-cell hyperproliferation, epithelial thickening, and eosinophilia. Notably, these characteristics are absent in ILC-deficient mice, whereas mice lacking IL-5 or eosinophils display epithelial defects, highlighting the pivotal role of ILC2s in EoE pathogenesis. Further investigations revealed increased amphiregulin (Areg) production by esophageal ILC2s in mice. The administration of Areg induced epithelial defects similar to those observed in EoE. Mechanistic studies using human esophageal cell lines revealed Areg-induced phosphorylation of epidermal growth factor receptor (EGFR). Significatntly, treatment with anti-Areg agents and EGFR inhibitors effectively attenuated EoE development, highlighting the therapeutic potential of targeting the Areg-EGFR axis.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 1","pages":"97-110"},"PeriodicalIF":21.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01242-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799544","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}

{"title":"Children exhibit a robust B-cell response to Omicron BA.2 after breakthrough infection with limited influence from the original antigenic sin","authors":"Zhiyang Ling, Zhangqian Zheng, Lingli Xu, Chunyan Yi, Xinran Dong, Xiaoqiong Gu, Xiaoyu Sun, Bingbing Wu, Bing Sun, Wenhao Zhou","doi":"10.1038/s41423-024-01241-y","DOIUrl":"10.1038/s41423-024-01241-y","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 1","pages":"127-130"},"PeriodicalIF":21.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766630","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}