美国ArsenalBio公司Jane L. Grogan和美国基因泰克公司Thomas D. Wu研究组合作发现外周血T细胞扩增可预测肿瘤浸润和临床反应。2020年2月26日，《自然》杂志在线发表了这一成果。
通过对患有不同类型癌症的患者进行RNA和T细胞受体深层单细胞测序，研究人员揭示了肿瘤、正常邻近组织和外周血中各种T细胞和T细胞受体的分布。足够的证据表明不仅在肿瘤内而且在正常的相邻组织中，效应样T细胞均呈克隆型扩增。具有这种克隆型扩增基因标记的患者对抗PDL1治疗的反应最佳。值得注意的是，在外周血中还可以检测到在肿瘤和正常相邻组织中发现的这种克隆型扩增，这提供了一种方便的患者识别方法。对该数据以及其它几个外部数据集的分析表明，来自肿瘤外部新鲜的、无穷尽的替代细胞补充了肿瘤内T细胞（尤其是反应性患者），这表明这些患者的癌症免疫周期持续激活并可能与临床反应有关。
研究人员表示，尽管阻断PD 1及其配体PDL 1相互作用的抗体在癌症治疗中取得了巨大的临床成功，但其涉及的机制仍然未知。在肿瘤免疫中阐述T细胞起源和命运的主要限制因素是缺乏癌症患者中T细胞个体克隆型分布的定量信息。
附：英文原文
Title: Peripheral T cell expansion predicts tumour infiltration and clinical response
Author: Thomas D. Wu, Shravan Madireddi, Patricia E. de Almeida, Romain Banchereau, Ying-Jiun J. Chen, Avantika S. Chitre, Eugene Y. Chiang, Hina Iftikhar, William E. OGorman, Amelia Au-Yeung, Chikara Takahashi, Leonard D. Goldstein, Chungkee Poon, Shilpa Keerthivasan, Denise E. de Almeida Nagata, Xiangnan Du, Hyang-Mi Lee, Karl L. Banta, Sanjeev Mariathasan, Meghna Das Thakur, Mahrukh A. Huseni, Marcus Ballinger, Ivette Estay, Patrick Caplazi, Zora Modrusan, Llia Delamarre, Ira Mellman, Richard Bourgon, Jane L. Grogan
Issue&Volume: 2020-02-26
Abstract: Despite the resounding clinical success in cancer treatment of antibodies that block the interaction of PD1 with its ligand PDL11, the mechanisms involved remain unknown. A major limitation to understanding the origin and fate of T cells in tumour immunity is the lack of quantitative information on the distribution of individual clonotypes of T cells in patients with cancer. Here, by performing deep single-cell sequencing of RNA and T cell receptors in patients with different types of cancer, we survey the profiles of various populations of T cells and T cell receptors in tumours, normal adjacent tissue, and peripheral blood. We find clear evidence of clonotypic expansion of effector-like T cells not only within the tumour but also in normal adjacent tissue. Patients with gene signatures of such clonotypic expansion respond best to anti-PDL1 therapy. Notably, expanded clonotypes found in the tumour and normal adjacent tissue can also typically be detected in peripheral blood, which suggests a convenient approach to patient identification. Analyses of our data together with several external datasets suggest that intratumoural T cells, especially in responsive patients, are replenished with fresh, non-exhausted replacement cells from sites outside the tumour, suggesting continued activity of the cancer immunity cycle in these patients, the acceleration of which may be associated with clinical response.
DOI: 10.1038/s41586-020-2056-8
Source: https://www.nature.com/articles/s41586-020-2056-8
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
