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T细胞识别的黑色素瘤抗原及其在免疫治疗中的应用。

Melanoma antigens recognized by T cells and their use for immunotherapy.

作者信息

Ohta Shigeki, Misawa Aya, Kyi-Tha-Thu Chaw, Matsumoto Naomi, Hirose Yoshie, Kawakami Yutaka

机构信息

Department of Immunology, School of Medicine, International University of Health and Welfare, Chiba, Japan.

Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.

出版信息

Exp Dermatol. 2023 Mar;32(3):297-305. doi: 10.1111/exd.14741. Epub 2023 Jan 30.

Abstract

Melanoma has been a prototype for cancer immunology research, and the mechanisms of anti-tumor T-cell responses have been extensively investigated in patients treated with various immunotherapies. Individual differences in cancer-immune status are defined mainly by cancer cell characteristics such as DNA mutations generating immunogenic neo-antigens, and oncogene activation causing immunosuppression, but also by patients' genetic backgrounds such as HLA types and genetic polymorphisms of immune related molecules, and environmental and lifestyle factors such as UV rays, smoking, gut microbiota and concomitant medications; these factors have an influence on the efficacy of immunotherapy. Recent comparative studies on responders and non-responders in immune-checkpoint inhibitor therapy using various new technologies including multi-omics analyses on genomic DNA, mRNA, metabolites and microbiota and single cell analyses of various immune cells have led to the advance of human tumor immunology and the development of new immunotherapy. Based on the new findings from these investigations, personalized cancer immunotherapies along with appropriate biomarkers and therapeutic targets are being developed for patients with melanoma. Here, we will discuss one of the essential subjects in tumor immunology: identification of immunogenic tumor antigens and their effective use in various immunotherapies including cancer vaccines and adoptive T-cell therapy.

摘要

黑色素瘤一直是癌症免疫学研究的典范,在接受各种免疫疗法治疗的患者中,抗肿瘤T细胞反应的机制已得到广泛研究。癌症免疫状态的个体差异主要由癌细胞特征决定,如产生免疫原性新抗原的DNA突变和导致免疫抑制的癌基因激活,也由患者的遗传背景决定,如HLA类型和免疫相关分子的基因多态性,以及环境和生活方式因素,如紫外线、吸烟、肠道微生物群和伴随用药;这些因素会影响免疫疗法的疗效。最近,利用包括对基因组DNA、mRNA、代谢物和微生物群的多组学分析以及对各种免疫细胞的单细胞分析等各种新技术,对免疫检查点抑制剂治疗中的应答者和非应答者进行的比较研究推动了人类肿瘤免疫学的进步和新免疫疗法的发展。基于这些研究的新发现,正在为黑色素瘤患者开发个性化癌症免疫疗法以及合适的生物标志物和治疗靶点。在此,我们将讨论肿瘤免疫学的一个重要主题:免疫原性肿瘤抗原的鉴定及其在包括癌症疫苗和过继性T细胞疗法在内的各种免疫疗法中的有效应用。

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