免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Melanoma antigens recognized by T cells and their use for immunotherapy.
Melanoma antigens recognized by T cells and their use for immunotherapy.
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黑色素瘤一直是癌症免疫学研究的原型,抗肿瘤T细胞反应的机制已在接受各种免疫治疗的患者中得到了广泛研究。癌症免疫状态的个体差异主要由癌细胞特征决定,例如产生免疫原性新抗原的DNA突变,以及导致免疫抑制的癌基因激活,但也由患者的遗传背景决定,例如HLA类型和免疫相关分子的遗传多态性,以及环境和生活方式因素,例如紫外线、吸烟、肠道微生物群和合并用药;这些因素对免疫治疗的疗效有影响。近期利用各种新技术对免疫检查点抑制剂治疗中应答者和无应答者进行的比较研究,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,推动了人类肿瘤免疫学的进步和新免疫疗法的开发。基于这些研究的新发现,正在为黑色素瘤患者开发伴随适当生物标志物和治疗靶点的个性化癌症免疫治疗。
在此,我们将讨论肿瘤免疫学中的一个核心课题: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细胞治疗在内的各种免疫治疗中的有效应用。
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.
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