肿瘤内具有组织驻留记忆表型的 CD8(+) T 细胞在乳腺癌中介导局部免疫和免疫检查点应答

CD8 + tumor-infiltrating lymphocytes with a tissue-resident memory T (T RM ) cell phenotype are associated with favorable prognosis in patients with triple-negative breast cancer (TNBC).

However, the relative contribution of CD8 + T RM 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 (T EX -like) and the other with a bona fide resident phenotype (T RM -like).

Treatment with anti-PD-1 and anti-CTLA-4 therapy resulted in expansion of these intratumoral populations, with the T RM -like subset displaying significantly enhanced cytotoxic capacity. T RM -like CD8 + T cells could also provide local immune protection against tumor rechallenge and a T RM gene signature extracted from tumor-free tissue was significantly associated with improved clinical outcomes in TNBC patients treated with checkpoint inhibitors.