美国国立卫生研究院Steven A. Rosenberg研究小组发现，干细胞样CD8 T细胞介导抗肿瘤的过继性细胞免疫疗法。2020年12月11日出版的《科学》杂志发表了这项成果。
研究人员表示，使用离体扩增的自体肿瘤浸润淋巴细胞（TIL）进行的过继性T细胞疗法（ACT）可以介导某些人类癌症的完全消退。目前尚不清楚TIL表型对TIL-ACT临床成功的影响。
通过对人类ACT的高维分析，研究人员发现，记忆祖先CD39阴性的干细胞表型（CD39-CD69-）与癌症的完全消退和TIL持续存在相关，而终末分化的CD39阳性状态（CD39+CD69+）与不良的TIL持久性相关。研究人员发现大多数抗肿瘤新抗原反应性TIL处于CD39+分化状态。但是，ACT应答者保留了ACT无应答者所缺乏的CD39-干细胞样新抗原特异性TIL库。肿瘤反应性干细胞样TIL在体内具有自我更新、扩增、持久性和优异的抗肿瘤反应能力。
这些数据表明，介导ACT反应的TIL亚群不同于抗肿瘤反应性的TIL亚群。
附：英文原文
Title: Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer
Author: Sri Krishna, Frank J. Lowery, Amy R. Copeland, Erol Bahadiroglu, Ratnadeep Mukherjee, Li Jia, James T. Anibal, Abraham Sachs, Serifat O. Adebola, Devikala Gurusamy, Zhiya Yu, Victoria Hill, Jared J. Gartner, Yong F. Li, Maria Parkhurst, Biman Paria, Pia Kvistborg, Michael C. Kelly, Stephanie L. Goff, Grégoire Altan-Bonnet, Paul F. Robbins, Steven A. Rosenberg
Issue&Volume: 2020/12/11
Abstract: Adoptive T cell therapy (ACT) using ex vivo–expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate complete regression of certain human cancers. The impact of TIL phenotypes on clinical success of TIL-ACT is currently unclear. Using high-dimensional analysis of human ACT products, we identified a memory-progenitor CD39-negative stem-like phenotype (CD39CD69) associated with complete cancer regression and TIL persistence and a terminally differentiated CD39-positive state (CD39+CD69+) associated with poor TIL persistence. Most antitumor neoantigen-reactive TILs were found in the differentiated CD39+ state. However, ACT responders retained a pool of CD39 stem-like neoantigen-specific TILs that was lacking in ACT nonresponders. Tumor-reactive stem-like TILs were capable of self-renewal, expansion, persistence, and superior antitumor response in vivo. These data suggest that TIL subsets mediating ACT response are distinct from TIL subsets enriched for antitumor reactivity.
DOI: 10.1126/science.abb9847
Source: https://science.sciencemag.org/content/370/6522/1328