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

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.

免疫检查点封锁可阻断T细胞活化的抑制信号，在治疗癌症方面已显示出巨大的成功，尽管仍然仅限于部分患者。迄今为止，临床上有效的CD8 + T细胞反应似乎主要针对源自肿瘤特异性突变的抗原，这些突变在癌症中累积，也称为新抗原。

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.

肿瘤抗原通过I类人类白细胞抗原（HLA-1）显示在细胞表面。为了引起有效的抗肿瘤应答，抗原呈递必须在两个不同的事件上成功：首先，癌症抗原必须被树突状细胞（DC）吸收并交叉呈递以用于CD8 + T细胞启动。其次，抗原必须直接由肿瘤呈递，才能被引发的CD8 + T细胞识别并杀死。在这两个步骤中，肿瘤都利用多种逃逸机制逃避免疫识别。在这里，我们审查了调节DC功能的肿瘤衍生因子，并总结了通过定量调节或定性改变肿瘤抗原表述来逃避免疫的证据。

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.

这些机制包括调节抗原表达，HLA-1表面水平，改变肿瘤细胞中抗原加工和呈递机制。最后，由于完全消除抗原呈递可导致自然杀伤（NK）细胞介导的肿瘤杀伤，因此，我们还讨论了肿瘤如何能够隐藏抗原呈递缺陷并仍能逃避NK细胞识别。