小柯机器人

韩国Penta Medix有限公司Jung Kyoon Choi、Dae-Yeon Cho和韩国成均馆大学医学院Se-Hoon Lee共同合作，近期取得重要工作进展。他们的最新研究发现MHC II免疫原性塑造了人类肿瘤的新表位格局。这一研究成果2023年1月9日在线发表于《自然—遗传学》杂志上。

据介绍，尽管在预测物理肽主要组织相容性复合物I（pMHC I）结合方面取得了进展，但鉴定功能性免疫原性新表位，尤其是MHC II，仍然具有挑战性。

通过对超过36000例免疫原性测定结果进行分析，研究人员开发了一种方法来鉴定结构排列有助于T细胞反应的pMHC。他们的方法预测了MHC II和MHC I的新表位，当应用于1200多个不同肿瘤类型的样本时，这些新表位对检查点阻断有反应。为了在单表位水平上研究自发免疫的选择，研究人员分析了9000多个初次治疗肿瘤的100多个免疫表型中超过2500万个突变的频谱。MHC II免疫原性在高免疫压力下特别降低了肿瘤中的变异频率，特别是在高TCR克隆性和MHC II表达的情况下。MHC I新表位也显示出类似的趋势，但仅限于特定组织类型。

总之，研究人员报告了MHC II限制的自然或治疗性T细胞反应性所施加的免疫选择。

附：英文原文

Title: MHC II immunogenicity shapes the neoepitope landscape in human tumors

Author: Kim, Jeong Yeon, Cha, Hongui, Kim, Kyeonghui, Sung, Changhwan, An, Jinhyeon, Bang, Hyoeun, Kim, Hyungjoo, Yang, Jin Ok, Chang, Suhwan, Shin, Incheol, Noh, Seung-Jae, Shin, Inkyung, Cho, Dae-Yeon, Lee, Se-Hoon, Choi, Jung Kyoon

Issue&Volume: 2023-01-09

Abstract: Despite advances in predicting physical peptide-major histocompatibility complex I (pMHC I) binding, it remains challenging to identify functionally immunogenic neoepitopes, especially for MHC II. By using the results of >36,000 immunogenicity assay, we developed a method to identify pMHC whose structural alignment facilitates T cell reaction. Our method predicted neoepitopes for MHC II and MHC I that were responsive to checkpoint blockade when applied to >1,200 samples of various tumor types. To investigate selection by spontaneous immunity at the single epitope level, we analyzed the frequency spectrum of >25 million mutations in >9,000 treatment-naive tumors with >100 immune phenotypes. MHC II immunogenicity specifically lowered variant frequencies in tumors under high immune pressure, particularly with high TCR clonality and MHC II expression. A similar trend was shown for MHC I neoepitopes, but only in particular tissue types. In summary, we report immune selection imposed by MHC II-restricted natural or therapeutic T cell reactivity.

DOI: 10.1038/s41588-022-01273-y

Source: https://www.nature.com/articles/s41588-022-01273-y

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex