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新工具可推断肿瘤中新抗原-T细胞相互作用的演变情况
作者:小柯机器人 发布时间:2022/10/30 19:52:57

美国德克萨斯大学研究小组开发出新工具netie,可用于推断肿瘤中新抗原-T细胞相互作用的演变情况。2022年10月27日,国际知名学术期刊《自然—方法学》在线发表了这一成果。

研究人员建立了一个层次化的贝叶斯模型,名为新抗原-T细胞相互作用估计(netie),用于推断肿瘤中新抗原-CD8+T细胞相互作用的历史。netie被系统地验证并应用于检查3219个肿瘤的分子模式,这些肿瘤是由18种癌症类型组成的。结果表明,随着时间的推移,免疫选择压力增加的肿瘤与具有活化相关表达特征的T细胞有关。研究人员还发现,免疫治疗后耗尽的细胞毒性T细胞亚群与治疗后新出现的肿瘤克隆有关。这些分析证明了netie如何能够审视个体新抗原重现和肿瘤分子谱之间的关系。
 
研究人员发现,在免疫压力随时间增加的肿瘤中,T细胞炎症基因表达谱(TIGEP)更能预测患者的预后,这揭示了T细胞和新抗原分布之间奇妙的协同作用。总的来说,研究人员提供了一个新的工具,能够揭示新抗原在每个肿瘤发展过程中留下的印记,并预测肿瘤在宿主免疫系统的进一步压力下将如何发展。
 
据悉,新抗原是细胞毒性T细胞抗肿瘤免疫反应的关键靶标,在影响肿瘤进展和免疫疗法治疗反应方面发挥着关键作用。然而,人们对新抗原和T细胞之间的相互作用如何最终影响癌症肿块的演变知之甚少。
 
附:英文原文

Title: Netie: inferring the evolution of neoantigen–T cell interactions in tumors

Author: Lu, Tianshi, Park, Seongoh, Han, Yi, Wang, Yunguan, Hubert, Shawna Marie, Futreal, P. Andy, Wistuba, Ignacio, Heymach, John V., Reuben, Alexandre, Zhang, Jianjun, Wang, Tao

Issue&Volume: 2022-10-27

Abstract: Neoantigens are the key targets of antitumor immune responses from cytotoxic T cells and play a critical role in affecting tumor progressions and immunotherapy treatment responses. However, little is known about how the interaction between neoantigens and T cells ultimately affects the evolution of cancerous masses. Here, we develop a hierarchical Bayesian model, named neoantigen–T cell interaction estimation (netie) to infer the history of neoantigen-CD8+ T cell interactions in tumors. Netie was systematically validated and applied to examine the molecular patterns of 3,219 tumors, compiled from a panel of 18 cancer types. We showed that tumors with an increase in immune selection pressure over time are associated with T cells that have an activation-related expression signature. We also identified a subset of exhausted cytotoxic T cells postimmunotherapy associated with tumor clones that newly arise after treatment. These analyses demonstrate how netie enables the interrogation of the relationship between individual neoantigen repertoires and the tumor molecular profiles. We found that a T cell inflammation gene expression profile (TIGEP) is more predictive of patient outcomes in the tumors with an increase in immune pressure over time, which reveals a curious synergy between T cells and neoantigen distributions. Overall, we provide a new tool that is capable of revealing the imprints left by neoantigens during each tumor’s developmental process and of predicting how tumors will progress under further pressure of the host’s immune system.

DOI: 10.1038/s41592-022-01644-7

Source: https://www.nature.com/articles/s41592-022-01644-7

期刊信息

Nature Methods:《自然—方法学》,创刊于2004年。隶属于施普林格·自然出版集团,最新IF:28.467
官方网址:https://www.nature.com/nmeth/
投稿链接:https://mts-nmeth.nature.com/cgi-bin/main.plex