Cellular &Molecular Immunology最新文献_第10页

Development of NK cell-based cancer immunotherapies through receptor engineering 通过受体工程开发基于 NK 细胞的癌症免疫疗法。

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-03-05 DOI: 10.1038/s41423-024-01145-x

Audrey Page, Nicolas Chuvin, Jenny Valladeau-Guilemond, Stéphane Depil

{"title":"Development of NK cell-based cancer immunotherapies through receptor engineering","authors":"Audrey Page, Nicolas Chuvin, Jenny Valladeau-Guilemond, Stéphane Depil","doi":"10.1038/s41423-024-01145-x","DOIUrl":"10.1038/s41423-024-01145-x","url":null,"abstract":"Natural killer (NK) cell-based immunotherapies are attracting increasing interest in the field of cancer treatment. Early clinical trials have shown promising outcomes, alongside satisfactory product efficacy and safety. Recent developments have greatly increased the therapeutic potential of NK cells by endowing them with enhanced recognition and cytotoxic capacities. This review focuses on surface receptor engineering in NK cell therapy and discusses its impact, challenges, and future directions. Most approaches are based on engineering with chimeric antigen receptors to allow NK cells to target specific tumor antigens independent of human leukocyte antigen restriction. This approach has increased the precision and potency of NK-mediated recognition and elimination of cancer cells. In addition, engineering NK cells with T-cell receptors also mediates the recognition of intracellular epitopes, which broadens the range of target peptides. Indirect tumor peptide recognition by NK cells has also been improved by optimizing immunoglobulin constant fragment receptor expression and signaling. Indeed, engineered NK cells have an improved ability to recognize and destroy target cells coated with specific antibodies, thereby increasing their antibody-dependent cellular cytotoxicity. The ability of NK cell receptor engineering to promote the expansion, persistence, and infiltration of transferred cells in the tumor microenvironment has also been explored. Receptor-based strategies for sustained NK cell functionality within the tumor environment have also been discussed, and these strategies providing perspectives to counteract tumor-induced immunosuppression. Overall, receptor engineering has led to significant advances in NK cell-based cancer immunotherapies. As technical challenges are addressed, these innovative treatments will likely reshape cancer immunotherapy.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01145-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038841","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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Author Correction: Tissue-resident macrophages exacerbate lung injury after remote sterile damage 作者更正：组织驻留的巨噬细胞会加重远端无菌损伤后的肺损伤。

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-03-01 DOI: 10.1038/s41423-024-01139-9

Hanhui Zhong, Jingjing Ji, Jinling Zhuang, Ziying Xiong, Pengyun Xie, Xiaolei Liu, Jundi Zheng, Wangli Tian, Xiaoyang Hong, Jing Tang

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Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance 边缘区 B 细胞的两个不同亚群表现出不同的抗体生成能力和放射抗性。

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-03-01 DOI: 10.1038/s41423-024-01126-0

Sujin Lee, Yeunjung Ko, Hyun Woo Lee, Won Joon Oh, Hun Gi Hong, Dinuka Ariyaratne, Se Jin Im, Tae Jin Kim

{"title":"Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance","authors":"Sujin Lee, Yeunjung Ko, Hyun Woo Lee, Won Joon Oh, Hun Gi Hong, Dinuka Ariyaratne, Se Jin Im, Tae Jin Kim","doi":"10.1038/s41423-024-01126-0","DOIUrl":"10.1038/s41423-024-01126-0","url":null,"abstract":"Marginal zone (MZ) B cells, which are splenic innate-like B cells that rapidly secrete antibodies (Abs) against blood-borne pathogens, are composed of heterogeneous subpopulations. Here, we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression levels. CD80high MZ B cells exhibited greater Ab-producing, proliferative, and IL-10-secreting capacities than did CD80low MZ B cells. Notably, CD80high MZ B cells survived 2-Gy whole-body irradiation, whereas CD80low MZ B cells were depleted by irradiation and then repleted with one month after irradiation. Depletion of CD80low MZ B cells led to accelerated development of type II collagen (CII)-induced arthritis upon immunization with bovine CII. CD80high MZ B cells exhibited higher expression of genes involved in proliferation, plasma cell differentiation, and the antioxidant response. CD80high MZ B cells expressed more autoreactive B cell receptors (BCRs) that recognized double-stranded DNA or CII, expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences, and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80low MZ B cells. Adoptive transfer experiments showed that CD21+CD23+ transitional 2 MZ precursors preferentially generated CD80low MZ B cells and that a proportion of CD80low MZ B cells were converted into CD80high MZ B cells; in contrast, CD80high MZ B cells stably remained CD80high MZ B cells. In summary, MZ B cells can be divided into two subpopulations according to their CD80 expression levels, Ab-producing capacity, radioresistance, and autoreactivity, and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995754","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}

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Targeting PHGDH reverses the immunosuppressive phenotype of tumor-associated macrophages through α-ketoglutarate and mTORC1 signaling 通过α-酮戊二酸和mTORC1信号转导，靶向PHGDH可逆转肿瘤相关巨噬细胞的免疫抑制表型。

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-02-27 DOI: 10.1038/s41423-024-01134-0

Zhengnan Cai, Wan Li, Sonja Hager, Jayne Louise Wilson, Leila Afjehi-Sadat, Elke H. Heiss, Thomas Weichhart, Petra Heffeter, Wolfram Weckwerth

{"title":"Targeting PHGDH reverses the immunosuppressive phenotype of tumor-associated macrophages through α-ketoglutarate and mTORC1 signaling","authors":"Zhengnan Cai, Wan Li, Sonja Hager, Jayne Louise Wilson, Leila Afjehi-Sadat, Elke H. Heiss, Thomas Weichhart, Petra Heffeter, Wolfram Weckwerth","doi":"10.1038/s41423-024-01134-0","DOIUrl":"10.1038/s41423-024-01134-0","url":null,"abstract":"Phosphoglycerate dehydrogenase (PHGDH) has emerged as a crucial factor in macromolecule synthesis, neutralizing oxidative stress, and regulating methylation reactions in cancer cells, lymphocytes, and endothelial cells. However, the role of PHGDH in tumor-associated macrophages (TAMs) is poorly understood. Here, we found that the T helper 2 (Th2) cytokine interleukin-4 and tumor-conditioned media upregulate the expression of PHGDH in macrophages and promote immunosuppressive M2 macrophage activation and proliferation. Loss of PHGDH disrupts cellular metabolism and mitochondrial respiration, which are essential for immunosuppressive macrophages. Mechanistically, PHGDH-mediated serine biosynthesis promotes α-ketoglutarate production, which activates mTORC1 signaling and contributes to the maintenance of an M2-like macrophage phenotype in the tumor microenvironment. Genetic ablation of PHGDH in macrophages from tumor-bearing mice results in attenuated tumor growth, reduced TAM infiltration, a phenotypic shift of M2-like TAMs toward an M1-like phenotype, downregulated PD-L1 expression and enhanced antitumor T-cell immunity. Our study provides a strong basis for further exploration of PHGDH as a potential target to counteract TAM-mediated immunosuppression and hinder tumor progression.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01134-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971112","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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NLRP3 inflammasome activation and NETosis positively regulate each other and exacerbate proinflammatory responses: implications of NETosis inhibition for acne skin inflammation treatment NLRP3 炎症小体激活与 NETosis 相互正向调节并加剧促炎反应：抑制 NETosis 对痤疮皮肤炎症治疗的意义

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-02-26 DOI: 10.1038/s41423-024-01137-x

Hyo Jeong Kim, Yun Sang Lee, Bok-Soon Lee, Chang-Hak Han, Sang Gyu Kim, Chul-Ho Kim

{"title":"NLRP3 inflammasome activation and NETosis positively regulate each other and exacerbate proinflammatory responses: implications of NETosis inhibition for acne skin inflammation treatment","authors":"Hyo Jeong Kim, Yun Sang Lee, Bok-Soon Lee, Chang-Hak Han, Sang Gyu Kim, Chul-Ho Kim","doi":"10.1038/s41423-024-01137-x","DOIUrl":"10.1038/s41423-024-01137-x","url":null,"abstract":"Inflammasomes are multiprotein complexes involved in the host immune response to pathogen infections. Thus, inflammasomes participate in many conditions, such as acne. Recently, it was shown that NETosis, a type of neutrophil cell death, is induced by bacterial infection and is involved in inflammatory diseases such as delayed wound healing in patients with diabetes. However, the relationship between inflammasomes and NETosis in the pathogenesis of inflammatory diseases has not been well studied. In this study, we determined whether NETosis is induced in P. acnes-induced skin inflammation and whether activation of the nucleotide-binding domain, leucine-rich family, and pyrin domain-containing-3 (NLRP3) inflammasome is one of the key factors involved in NETosis induction in a mouse model of acne skin inflammation. We found that NETosis was induced in P. acnes-induced skin inflammation in mice and that inhibition of NETosis ameliorated P. acnes-induced skin inflammation. In addition, our results demonstrated that inhibiting inflammasome activation could suppress NETosis induction in mouse skin. These results indicate that inflammasomes and NETosis can interact with each other to induce P. acnes-induced skin inflammation and suggest that targeting NETosis could be a potential treatment for inflammasome-mediated diseases as well as NETosis-related diseases.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139968449","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}

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Coming of age: the formation and function of age-associated B cells 成年：与年龄有关的 B 细胞的形成和功能

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-02-26 DOI: 10.1038/s41423-024-01143-z

Ke Rui, Nan Che, Kongyang Ma, Hejian Zou, Fan Xiao, Liwei Lu

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Inactivation of TGF-β signaling in CAR-T cells 使 CAR-T 细胞中的 TGF-β 信号失活

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-02-26 DOI: 10.1038/s41423-023-01123-9

Zaopeng Yang, Yang-Xin Fu

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CD4+ T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors CD4+ T 细胞产生 IFN-I，许可 cDC1s 诱导人类肿瘤中的细胞毒性 T 细胞活性

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-02-21 DOI: 10.1038/s41423-024-01133-1

Xin Lei, Daniël C. de Groot, Marij J. P. Welters, Tom de Wit, Ellen Schrama, Hans van Eenennaam, Saskia J. Santegoets, Timo Oosenbrug, Annemarthe van der Veen, Joris L. Vos, Charlotte L. Zuur, Noel F. C. C. de Miranda, Heinz Jacobs, Sjoerd H. van der Burg, Jannie Borst, Yanling Xiao

{"title":"CD4+ T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors","authors":"Xin Lei, Daniël C. de Groot, Marij J. P. Welters, Tom de Wit, Ellen Schrama, Hans van Eenennaam, Saskia J. Santegoets, Timo Oosenbrug, Annemarthe van der Veen, Joris L. Vos, Charlotte L. Zuur, Noel F. C. C. de Miranda, Heinz Jacobs, Sjoerd H. van der Burg, Jannie Borst, Yanling Xiao","doi":"10.1038/s41423-024-01133-1","DOIUrl":"10.1038/s41423-024-01133-1","url":null,"abstract":"CD4+ T cells can \"help” or \"license” conventional type 1 dendritic cells (cDC1s) to induce CD8+ cytotoxic T lymphocyte (CTL) anticancer responses, as proven in mouse models. We recently identified cDC1s with a transcriptomic imprint of CD4+ T-cell help, specifically in T-cell-infiltrated human cancers, and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy. Here, we delineate the mechanism of cDC1 licensing by CD4+ T cells in humans. Activated CD4+ T cells produce IFNβ via the STING pathway, which promotes MHC-I antigen (cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer responses. In cooperation with CD40 ligand (L), IFNβ also optimizes the costimulatory and other functions of cDC1s required for CTL response induction. IFN-I-producing CD4+ T cells are present in diverse T-cell-infiltrated cancers and likely deliver “help” signals to CTLs locally, according to their transcriptomic profile and colocalization with “helped/licensed” cDCs and tumor-reactive CD8+ T cells. In agreement with this scenario, the presence of IFN-I-producing CD4+ T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01133-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139925725","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

Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing 不同步的丁酵素分子决定了癌细胞对 Vγ9Vδ2 T 细胞杀伤的逃避。

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-02-20 DOI: 10.1038/s41423-024-01135-z

Zeguang Wu, Qiezhong Lamao, Meichao Gu, Xuanxuan Jin, Ying Liu, Feng Tian, Ying Yu, Pengfei Yuan, Shuaixin Gao, Thomas S. Fulford, Adam P. Uldrich, Catherine CL Wong, Wensheng Wei

{"title":"Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing","authors":"Zeguang Wu, Qiezhong Lamao, Meichao Gu, Xuanxuan Jin, Ying Liu, Feng Tian, Ying Yu, Pengfei Yuan, Shuaixin Gao, Thomas S. Fulford, Adam P. Uldrich, Catherine CL Wong, Wensheng Wei","doi":"10.1038/s41423-024-01135-z","DOIUrl":"10.1038/s41423-024-01135-z","url":null,"abstract":"Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites. In our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells, we performed a comprehensive genome-scale CRISPR screening of cancer cells. We found that four molecules belonging to the butyrophilin (BTN) family, specifically BTN2A1, BTN3A1, BTN3A2, and BTN3A3, are critically important and play unique, nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T cells. The coordinated function of these BTN molecules was driven by synchronized gene expression, which was regulated by IFN-γ signaling and the RFX complex. Additionally, an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer cells. Through our research, we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T cells. Moreover, our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905189","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}

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CD200Rhigh neutrophils with dysfunctional autophagy establish systemic immunosuppression by increasing regulatory T cells 自噬功能失调的 CD200R 高中性粒细胞会通过增加调节性 T 细胞来建立全身免疫抑制。

IF 24.1 1区医学

Cellular &Molecular Immunology Pub Date : 2024-02-05 DOI: 10.1038/s41423-024-01136-y

Ye Seon Kim, Yu Sun Jeong, Geon Ho Bae, Ji Hyeon Kang, Mingyu Lee, Brian A. Zabel, Yoe-Sik Bae

{"title":"CD200Rhigh neutrophils with dysfunctional autophagy establish systemic immunosuppression by increasing regulatory T cells","authors":"Ye Seon Kim, Yu Sun Jeong, Geon Ho Bae, Ji Hyeon Kang, Mingyu Lee, Brian A. Zabel, Yoe-Sik Bae","doi":"10.1038/s41423-024-01136-y","DOIUrl":"10.1038/s41423-024-01136-y","url":null,"abstract":"Distinct neutrophil populations arise during certain pathological conditions. The generation of dysfunctional neutrophils during sepsis and their contribution to septicemia-related systemic immune suppression remain unclear. In this study, using an experimental sepsis model that features immunosuppression, we identified a novel population of pathogenic CD200Rhigh neutrophils that are generated during the initial stages of sepsis and contribute to systemic immune suppression by enhancing regulatory T (Treg) cells. Compared to their CD200Rlow counterparts, sepsis-generated CD200Rhigh neutrophils exhibit impaired autophagy and dysfunction, with reduced chemotactic migration, superoxide anion production, and TNF-α production. Increased soluble CD200 blocks autophagy and neutrophil maturation in the bone marrow during experimental sepsis, and recombinant CD200 treatment in vitro can induce neutrophil dysfunction similar to that observed in CD200Rhigh neutrophils. The administration of an α-CD200R antibody effectively reversed neutrophil dysfunction by enhancing autophagy and protecting against a secondary infection challenge, leading to increased survival. Transcriptome analysis revealed that CD200Rhigh neutrophils expressed high levels of Igf1, which elicits the generation of Treg cells, while the administration of an α-CD200R antibody inhibited Treg cell generation in a secondary infection model. Taken together, our findings revealed a novel CD200Rhigh neutrophil population that mediates the pathogenesis of sepsis-induced systemic immunosuppression by generating Treg cells.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":null,"pages":null},"PeriodicalIF":24.1,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680666","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