当前位置: X-MOL 学术Cancer Cell › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
An activation to memory differentiation trajectory of tumor-infiltrating lymphocytes informs metastatic melanoma outcomes
Cancer Cell ( IF 48.8 ) Pub Date : 2022-05-09 , DOI: 10.1016/j.ccell.2022.04.005
Abhinav Jaiswal 1 , Akanksha Verma 2 , Ruth Dannenfelser 3 , Marit Melssen 4 , Itay Tirosh 5 , Benjamin Izar 6 , Tae-Gyun Kim 7 , Christopher J Nirschl 8 , K Sanjana P Devi 9 , Walter C Olson 10 , Craig L Slingluff 4 , Victor H Engelhard 11 , Levi Garraway 12 , Aviv Regev 13 , Kira Minkis 9 , Charles H Yoon 14 , Olga Troyanskaya 15 , Olivier Elemento 2 , Mayte Suárez-Fariñas 16 , Niroshana Anandasabapathy 17
Affiliation  

There is a need for better classification and understanding of tumor-infiltrating lymphocytes (TILs). Here, we applied advanced functional genomics to interrogate 9,000 human tumors and multiple single-cell sequencing sets using benchmarked T cell states, comprehensive T cell differentiation trajectories, human and mouse vaccine responses, and other human TILs. Compared with other T cell states, enrichment of T memory/resident memory programs was observed across solid tumors. Trajectory analysis of single-cell melanoma CD8+ TILs also identified a high fraction of memory/resident memory-scoring TILs in anti-PD-1 responders, which expanded post therapy. In contrast, TILs scoring highly for early T cell activation, but not exhaustion, associated with non-response. Late/persistent, but not early activation signatures, prognosticate melanoma survival, and co-express with dendritic cell and IFN-γ response programs. These data identify an activation-like state associated to poor response and suggest successful memory conversion, above resuscitation of exhaustion, is an under-appreciated aspect of successful anti-tumoral immunity.



中文翻译:


肿瘤浸润淋巴细胞记忆分化轨迹的激活可告知转移性黑色素瘤的结果



需要更好地分类和理解肿瘤浸润淋巴细胞(TIL)。在这里,我们应用先进的功能基因组学,使用基准 T 细胞状态、全面的 T 细胞分化轨迹、人类和小鼠疫苗反应以及其他人类 TIL 来询问 9,000 个人类肿瘤和多个单细胞测序集。与其他 T 细胞状态相比,在实体瘤中观察到 T 记忆/驻留记忆程序的丰富。单细胞黑色素瘤 CD8 + TIL 的轨迹分析还发现,抗 PD-1 应答者中有很高比例的记忆/常驻记忆评分 TIL,且在治疗后会扩大。相比之下,TIL 在早期 T 细胞激活方面得分较高,但在与无反应相关的衰竭方面得分较低。晚期/持续而非早期的激活特征可预测黑色素瘤的存活,并与树突状细胞和 IFN-γ 反应程序共表达。这些数据确定了与不良反应相关的类激活状态,并表明成功的记忆转换(高于疲劳复苏)是成功抗肿瘤免疫的一个未被充分认识的方面。

更新日期:2022-05-09
down
wechat
bug