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

Authors:

• Virassamy, Balaji
• Caramia, Franco
• Savas, Peter
• Sant, Sneha
• Wang, Jianan
• Christo, Susan N.
• Byrne, Ann
• Clarke, Kylie
• Brown, Emmaline
• Teo, Zhi Ling
• von Scheidt, Bianca
• Freestone, David
• Gandolfo, Luke C.
• Weber, Karsten
• Teply-Szymanski, Julia
• Li, Ran
• Luen, Stephen J.
• Denkert, Carsten
• Loibl, Sibylle
• Lucas, Olivia
• Swanton, Charles
• Speed, Terence P.
• Darcy, Phillip K.
• Neeson, Paul J.
• Mackay, Laura K.
• Loi, Sherene

Details:

Cancer Cell, Volume 41, Issue 3, 2023-03-13

Article Link: Click here

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.