Different tumour-resident memory T-cell subsets regulate responses to anti-PD-1 and anti-CTLA-4 cancer immunotherapies.

ABSTRACT: The involvement of tumour-resident memory T (T_RM) cells in responses to immune checkpoint inhibitors remains unclear. Here, we show that while CD103⁺CD8 T_RM cells are involved in response to PD-1 blockade, CD49a⁺CD4 T_RM cells are required for the response to anti-CTLA-4. Using preclinical mouse models, we demonstrate that the benefits of anti-PD-1 treatment are compromised in animals challenged with anti-CD8 and anti-CD103 blocking antibodies. By contrast, the benefits of anti-CTLA-4 are decreased by anti-CD4 and anti-CD49a neutralizing antibodies. Single-cell RNA sequencing on tumour-infiltrating T-lymphocytes (TIL) reveals a CD49a⁺CD4 T_RM signature, enriched in Ctla-4 transcripts, exacerbated upon anti-CTLA-4. C

SUBMITTER: Damei I 

PROVIDER: S-EPMC12216323 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature