美国威尔康奈尔医学院皮肤科Niroshana Anandasabapathy团队发现肿瘤浸润淋巴细胞 (TIL)对记忆分化轨迹的激活预示转移性黑色素瘤预后。相关论文于2022年5月9日发表在《癌细胞》杂志上。

他们应用先进的功能基因组学，使用基准 T 细胞状态、综合 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/常驻记忆程序的富集。单细胞黑色素瘤 CD8+ TIL 的轨迹分析还确定了抗 PD-1 应答者中高比例的记忆/常驻记忆评分 TIL，这扩大了治疗后的范围。

相比之下，TILs 在早期 T 细胞激活方面得分很高，但不是衰竭，与无应答相关。晚期/持续性，但不是早期激活特征，预示着黑色素瘤的存活，并与树突状细胞和 IFN-γ 应答程序共同表达。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，高于衰竭的复苏，是成功的抗肿瘤免疫的一个未被充分认识的方面。

据悉，还需要对TIL进行更好的分类和理解。

附：英文原文

Title: An activation to memory differentiation trajectory of tumor-infiltrating lymphocytes informs metastatic melanoma outcomes

Author: Abhinav Jaiswal, Akanksha Verma, Ruth Dannenfelser, Marit Melssen, Itay Tirosh, Benjamin Izar, Tae-Gyun Kim, Christopher J. Nirschl, K. Sanjana P. Devi, Walter C. Olson, Craig L. Slingluff, Victor H. Engelhard, Levi Garraway, Aviv Regev, Kira Minkis, Charles H. Yoon, Olga Troyanskaya, Olivier Elemento, Mayte Suárez-Farias, Niroshana Anandasabapathy

Issue&Volume: 2022/05/09

Abstract: 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.

DOI: 10.1016/j.ccell.2022.04.005

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00167-2