澳大利亚墨尔本大学Sherene Loi和Laura K. Mackay等研究组合作揭示，具有组织常驻记忆表型的肿瘤内CD8+ T细胞介导乳腺癌的局部免疫和免疫检查点反应。这一研究成果发表在2023年2月23日出版的国际学术期刊《癌细胞》上。

他们表明小鼠乳腺肿瘤中的肿瘤内CD8 + T细胞在转录上与三阴性乳腺癌（TNBC）患者的细胞相似。表型和转录研究建立了两个肿瘤内亚群：一个更富含终末衰竭标志物（TEX样），另一个具有真正的常驻表型（组织驻留记忆 T（TRM）样）。抗PD-1和抗CTLA-4治疗导致这些肿瘤内群体的扩张，TRM样亚群显示出显著增强的细胞毒性能力。TRM样CD8 + T细胞还可以提供针对肿瘤再挑战的局部免疫保护，并且从无肿瘤组织中提取的TRM基因标记与接受检查点抑制剂治疗的TNBC患者的临床预后改善显著相关。

据介绍，具有TRM细胞表型的 CD8+ 肿瘤浸润淋巴细胞与TNBC患者的良好预后相关。然而，CD8 + TRM细胞对乳腺癌抗肿瘤免疫和免疫检查点阻断功效的相对贡献仍然未知。

附：英文原文

Title: Intratumoral CD8+ T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancer

Author: 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

Issue&Volume: 2023-02-23

Abstract: CD8+ tumor-infiltrating lymphocytes with a tissue-resident memory T (TRM) cell phenotype are associated with favorable prognosis in patients with triple-negativebreast cancer (TNBC). However, the relative contribution of CD8+ TRM cells to anti-tumor immunity and immune checkpoint blockade efficacy in breast cancerremains 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 ofthese 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 anda TRM gene signature extracted from tumor-free tissue was significantly associated withimproved clinical outcomes in TNBC patients treated with checkpoint inhibitors.

DOI: 10.1016/j.ccell.2023.01.004

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00004-1