原句：Intratumoral CD8+ T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancer. 简化汉语：组织内CD8+T细胞以组织驻留记忆表型介导了乳腺癌中的局部免疫和免疫检查点反应。
Intratumoral CD8+ T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancer.
发表日期：2023 Feb 08
作者：
Balaji Virassamy, Franco Caramia, Peter Savas, Sneha Sant, Jianan Wang, Susan N Christo, Ann Byrne, Kylie Clarke, Emmaline Brown, Zhi Ling Teo, Bianca von Scheidt, David Freestone, Luke C Gandolfo, Karsten Weber, Julia Teply-Szymanski, Ran Li, Stephen J Luen, Carsten Denkert, Sibylle Loibl, Olivia Lucas, Charles Swanton, Terence P Speed, Phillip K Darcy, Paul J Neeson, Laura K Mackay, Sherene Loi
来源：
CANCER CELL
摘要：
具有组织驻留记忆性T细胞（TRM）细胞表型的CD8 + 肿瘤浸润淋巴细胞与三阴性乳腺癌（TNBC）患者良好预后有关。然而，CD8 + TRM细胞在乳腺癌中的抗肿瘤免疫和免疫检查点阻断疗效的相对贡献尚不清楚。在这里，我们展示了小鼠乳腺肿瘤内的CD8 + T细胞在转录上类似于TNBC患者的CD8 + T细胞。表型和转录学研究确定了两个肿瘤内亚种群：一个更富含末端耗竭标记（TEX类似）的亚群和另一个具有真正的居留表型（TRM类似）。抗PD-1和抗CTLA-4治疗导致这些肿瘤内人群的扩张，TRM类似的亚集显示出显着增强的细胞毒性能力。TRM类似的CD8 + T细胞还可以对抗肿瘤再挑战提供局部免疫保护，从无肿瘤组织中提取的TRM基因签名与接受检查点抑制剂治疗的TNBC患者的临床预后显着相关。版权所有©2023 Elsevier Inc.保留所有权利。
CD8+ tumor-infiltrating lymphocytes with a tissue-resident memory T (TRM) cell phenotype are associated with favorable prognosis in patients with triple-negative breast cancer (TNBC). However, the relative contribution of CD8+ TRM cells to anti-tumor immunity and immune checkpoint blockade efficacy in breast cancer remains unknown. Here, we show that intratumoral CD8+ T cells in murine mammary tumors transcriptionally resemble those from TNBC patients. Phenotypic and transcriptional studies established two intratumoral sub-populations: one more enriched in markers of terminal exhaustion (TEX-like) and the other with a bona fide resident phenotype (TRM-like). Treatment with anti-PD-1 and anti-CTLA-4 therapy resulted in expansion of these intratumoral populations, with the TRM-like subset displaying significantly enhanced cytotoxic capacity. TRM-like CD8+ T cells could also provide local immune protection against tumor rechallenge and a TRM gene signature extracted from tumor-free tissue was significantly associated with improved clinical outcomes in TNBC patients treated with checkpoint inhibitors.Copyright © 2023 Elsevier Inc. All rights reserved.