Neoantigen-specific cytotoxic Tr1 CD4 T cells suppress cancer immunotherapy.

ABSTRACT: CD4⁺ T cells can either enhance or inhibit tumour immunity. Although regulatory T cells have long been known to impede antitumour responses^1-5, other CD4⁺ T cells have recently been implicated in inhibiting this response^6,7. Yet, the nature and function of the latter remain unclear. Here, using vaccines containing MHC class I (MHC-I) neoantigens (neoAgs) and different doses of tumour-derived MHC-II neoAgs, we discovered that whereas the inclusion of vaccines with low doses of MHC-II-restricted peptides (LDVax) promoted tumour rejection, vaccines containing high doses of the same MHC-II neoAgs (HDVax) inhibited rejection. Characterization of the inhibitory cells induced by HDVax identified them as type 1 regulatory T (Tr1) cells expressing IL-10,

SUBMITTER: Sultan H 

PROVIDER: S-EPMC11291290 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature