美国圣路易斯华盛顿大学医学院Robert D. Schreiber课题组在研究中取得进展。他们发现MHC-II新抗原改变肿瘤免疫和免疫疗法的响应。相关论文2019年10月23日在线发表于《自然》杂志。
研究人员发现，即使在不表达主要组织相容性复合体（MHC）II类分子的肿瘤中，自发性和免疫疗法诱导的抗肿瘤反应也需要肿瘤抗原特异性CD8阳性和CD4阳性T细胞的活性。另外，在成功排斥的位点需要肿瘤细胞表达MHC-II限制性抗原，这表明CD4阳性T细胞的激活也必须在肿瘤微环境中发生。这些发现表明，MHC-II限制性新抗原在抗肿瘤反应中具有关键功能，与MHC-I限制性新抗原并不重叠，因此这一点在寻找最受益于免疫治疗的患者时需要考虑。
据介绍，免疫系统消除和塑造肿瘤免疫原性的能力决定了癌症免疫改变的过程。诸如靶向免疫检查点分子的免疫疗法可用于增强免疫介导的肿瘤消除，并能够导致对先前治疗无反应的癌症患者产生持久反应。但是，只有一部分患者可以从免疫疗法中受益，并且需要更多地了解成功治疗所需的因素。尽管目前的研究已经明确建立了肿瘤新抗原特异性CD8 阳性T细胞在肿瘤排斥中的作用，但其他T细胞亚群的作用却很少受到关注。
附：英文原文
Title: MHC-II neoantigens shape tumour immunity and response to immunotherapy
Author: Elise Alspach, Danielle M. Lussier, Alexander P. Miceli, Ilya Kizhvatov, Michel DuPage, Adrienne M. Luoma, Wei Meng, Cheryl F. Lichti, Ekaterina Esaulova, Anthony N. Vomund, Daniele Runci, Jeffrey P. Ward, Matthew M. Gubin, Ruan F. V. Medrano, Cora D. Arthur, J. Michael White, Kathleen C. F. Sheehan, Alex Chen, Kai W. Wucherpfennig, Tyler Jacks, Emil R. Unanue, Maxim N. Artyomov, Robert D. Schreiber
Issue&Volume: 2019-10-23
Abstract: The ability of the immune system to eliminate and shape the immunogenicity of tumours defines the process of cancer immunoediting1. Immunotherapies such as those that target immune checkpoint molecules can be used to augment immune-mediated 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 needed2,3,4. Although the role of tumour neoantigen-specific CD8+ T cells in tumour rejection is well established5,6,7,8,9, 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.
DOI: 10.1038/s41586-019-1671-8
Source: https://www.nature.com/articles/s41586-019-1671-8
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
