MHC-II neoantigens shape tumour immunity and response to immunotherapy
MHC-II neoantigens shape tumour immunity and response to immunotherapy
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DOI：
10.1038/s41586-019-1671-8
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发表时间：
2019-10-31
期刊：
影响因子：
64.8
通讯作者：
Schreiber, Robert D.
中科院分区：
文献类型：
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作者：
Alspach, Elise;Lussier, Danielle M.;Schreiber, Robert D.
免疫系统消除和塑造肿瘤免疫原性的能力定义了癌症免疫编辑的过程（1）。诸如靶向免疫检查点分子的免疫疗法可用于增强免疫疗法消除肿瘤，并导致对先前治疗没有反应的癌症患者的持久反应。但是，只有一部分患者受益于免疫疗法，并且需要更多关于成功治疗所需的知识（2-4）。尽管肿瘤新抗原特异性CD8（+）T细胞在肿瘤排斥反应中的作用已得到很好的确定（5-9），但其他T细胞的作用却较少受到关注。在这里，我们表明自发和免疫疗法诱导的抗肿瘤反应都需要肿瘤 - 抗原特异性CD8（+）和CD4（+）T细胞的活性，即使在不表达主要组织相容性复合物（MHC）II类的肿瘤中分子。此外，在成功排斥反应的部位需要肿瘤细胞的MHC II类限制抗原表达，这表明CD4（+）T细胞的激活也必须发生在肿瘤微环境中。这些发现表明，MHC II限制的新抗原在抗肿瘤反应中具有关键功能，而与MHC I类限制的新抗原的抗肿瘤反应无关，因此在识别将从免疫疗法中受益最大的患者时需要考虑。
The ability of the immune system to eliminate and shape the immunogenicity of tumours defines the process of cancer immunoediting(1). Immunotherapies such as those that target immune checkpoint molecules can be used to augment immunemediated elimination of tumours and have resulted in durable responses in patients with cancer that did not respond to previous treatments. However, only a subset of patients benefit from immunotherapy and more knowledge about what is required for successful treatment is needed(2-4). Although the role of tumour neoantigen-specific CD8(+) T cells in tumour rejection is well established(5-9), the roles of other subsets of T cells have received less attention. Here we show that spontaneous and immunotherapy-induced anti-tumour responses require the activity of both tumour-antigen-specific CD8(+) and CD4(+) T cells, even in tumours that do not express major histocompatibility complex (MHC) class II molecules. In addition, the expression of MHC class II-restricted antigens by tumour cells is required at the site of successful rejection, indicating that activation of CD4(+) T cells must also occur in the tumour microenvironment. These findings suggest that MHC class II-restricted neoantigens have a key function in the anti-tumour response that is nonoverlapping with that of MHC class I-restricted neoantigens and therefore needs to be considered when identifying patients who will most benefit from immunotherapy.