Intratumoral CD8+ T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancer
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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 Toggle all authors (26)
Abstract
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 details
Journal Cancer Cell
Volume 41
Issue number 3
Pages 585-601.e8
Available online
Publication date
Full text links
Publisher website (DOI) 10.1016/j.ccell.2023.01.004
Europe PubMed Central 36827978
Pubmed 36827978