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.