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

Menée à l'aide de lignées cellulaires, de modèles murins et de données de séquençage d'ARNs tumoraux provenant de patientes atteintes d'un cancer du sein triple négatif et non métastatique, cette étude met en évidence le rôle, dans la protection immunitaire locale contre la tumeur et l'efficacité des inhibiteurs de point de contrôle immunitaire, d'une sous-population de lymphocytes T CD8+ intratumoraux présentant un phénotype ressemblant à celui des cellules T résidentes mémoires

Résumé en anglais

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.