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


  • 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


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.