Intratumoral CD8+ T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancerMore about Open Access at the Crick
Authors listBalaji 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
Toggle all authors (26)
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.
Journal Cancer Cell
Issue number 3