文章：

癌症中的抗原呈递：对肿瘤免疫原性和免疫逃避的认识

Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion

原文发布日期：2021-03-09

DOI: 10.1038/s41568-021-00339-z

类型: Review Article

开放获取: 否

英文摘要：

Immune checkpoint blockade, which blocks inhibitory signals of T cell activation, has shown tremendous success in treating cancer, although success still remains limited to a fraction of patients. To date, clinically effective CD8+ T cell responses appear to target predominantly antigens derived from tumour-specific mutations that accumulate in cancer, also called neoantigens. Tumour antigens are displayed on the surface of cells by class I human leukocyte antigens (HLA-I). To elicit an effective antitumour response, antigen presentation has to be successful at two distinct events: first, cancer antigens have to be taken up by dendritic cells (DCs) and cross-presented for CD8+ T cell priming. Second, the antigens have to be directly presented by the tumour for recognition by primed CD8+ T cells and killing. Tumours exploit multiple escape mechanisms to evade immune recognition at both of these steps. Here, we review the tumour-derived factors modulating DC function, and we summarize evidence of immune evasion by means of quantitative modulation or qualitative alteration of the antigen repertoire presented on tumours. These mechanisms include modulation of antigen expression, HLA-I surface levels, alterations in the antigen processing and presentation machinery in tumour cells. Lastly, as complete abrogation of antigen presentation can lead to natural killer (NK) cell-mediated tumour killing, we also discuss how tumours can harbour antigen presentation defects and still evade NK cell recognition.

摘要翻译： 

免疫检查点阻断通过抑制T细胞活化的负向信号，在癌症治疗中取得了巨大成功，尽管其疗效仍仅限于部分患者。迄今为止，临床有效的CD8+ T细胞应答主要靶向源于肿瘤特异性突变的抗原（即新抗原），这些突变在癌症中不断积累。肿瘤抗原通过I类人类白细胞抗原（HLA-I）呈现在细胞表面。要引发有效的抗肿瘤应答，抗原呈递必须在两个关键环节成功实现：首先，树突状细胞（DCs）需摄取癌症抗原并通过交叉呈递激活CD8+ T细胞；其次，肿瘤需直接呈递抗原以供活化的CD8+ T细胞识别和杀伤。肿瘤利用多种逃逸机制在这两个步骤中规避免疫识别。本文综述了调节DC功能的肿瘤源性因子，并总结了通过定量调控或定性改变肿瘤抗原库实现免疫逃逸的证据。这些机制包括抗原表达调控、HLA-I表面水平改变，以及肿瘤细胞中抗原加工和呈递机制的 alterations。最后，鉴于抗原呈递的完全缺失可能引发自然杀伤（NK）细胞介导的肿瘤杀伤，我们还探讨了肿瘤如何在存在抗原呈递缺陷的情况下仍能逃避NK细胞识别。

原文链接：

Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion