Tumor-associated macrophages promote intratumoral conversion of conventional CD4⁺ T cells into regulatory T cells via PD-1 signalling.

ABSTRACT: While regulatory T cells (T_regs) and macrophages have been recognized as key orchestrators of cancer-associated immunosuppression, their cellular crosstalk within tumors has been poorly characterized. Here, using spontaneous models for breast cancer, we demonstrate that tumor-associated macrophages (TAMs) contribute to the intratumoral accumulation of T_regs by promoting the conversion of conventional CD4⁺ T cells (T_convs) into T_regs. Mechanistically, two processes were identified that independently contribute to this process. While TAM-derived TGF-β directly promotes the conversion of CD4⁺ T_convs into T_regsin vitro, we additionally show that TAMs enhance PD-1 expression on CD4⁺ T cells

SUBMITTER: Kos K 

PROVIDER: S-EPMC9037432 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature