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Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer.
Journal of Experimental Medicine ( IF 15.3 ) Pub Date : 2019-06-21 , DOI: 10.1084/jem.20190249
James Clarke 1, 2 , Bharat Panwar 1 , Ariel Madrigal 1 , Divya Singh 1 , Ravindra Gujar 1 , Oliver Wood 2 , Serena J Chee 2, 3 , Simon Eschweiler 1 , Emma V King 2, 4 , Amiera S Awad 3, 5 , Christopher J Hanley 2 , Katy J McCann 2 , Sourya Bhattacharyya 1 , Edwin Woo 3 , Aiman Alzetani 3 , Grégory Seumois 1 , Gareth J Thomas 2 , Anusha-Preethi Ganesan 1 , Peter S Friedmann 5 , Tilman Sanchez-Elsner 5 , Ferhat Ay 1 , Christian H Ottensmeier 6 , Pandurangan Vijayanand 5, 7, 8
Affiliation  

High numbers of tissue-resident memory T (TRM) cells are associated with better clinical outcomes in cancer patients. However, the molecular characteristics that drive their efficient immune response to tumors are poorly understood. Here, single-cell and bulk transcriptomic analysis of TRM and non-TRM cells present in tumor and normal lung tissue from patients with lung cancer revealed that PD-1-expressing TRM cells in tumors were clonally expanded and enriched for transcripts linked to cell proliferation and cytotoxicity when compared with PD-1-expressing non-TRM cells. This feature was more prominent in the TRM cell subset coexpressing PD-1 and TIM-3, and it was validated by functional assays ex vivo and also reflected in their chromatin accessibility profile. This PD-1+TIM-3+ TRM cell subset was enriched in responders to PD-1 inhibitors and in tumors with a greater magnitude of CTL responses. These data highlight that not all CTLs expressing PD-1 are dysfunctional; on the contrary, TRM cells with PD-1 expression were enriched for features suggestive of superior functionality.

中文翻译:

人肺癌组织驻留记忆T细胞的单细胞转录组学分析。

在癌症患者中,大量的组织驻留记忆T(TRM)细胞与更好的临床结局相关。然而,人们对驱动其对肿瘤的有效免疫反应的分子特征了解甚少。在这里,对肺癌患者的肿瘤和正常肺组织中存在的TRM和非TRM细胞的单细胞和大量转录组分析显示,肿瘤中表达PD-1的TRM细胞被克隆扩增并富集了与细胞增殖有关的转录本与表达PD-1的非TRM细胞相比具有更高的细胞毒性和细胞毒性。此特征在共表达PD-1和TIM-3的TRM细胞亚群中更为突出,并且已通过离体功能测定得到验证,并且也反映在它们的染色质可及性方面。该PD-1 + TIM-3 + TRM细胞亚群富含对PD-1抑制剂的应答剂以及具有更大CTL应答量的肿瘤。这些数据表明,并非所有表达PD-1的CTL都功能失调。相反,具有PD-1表达的TRM细胞富含暗示优越功能的特征。
更新日期:2019-09-03
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