Immunosuppressive Myeloid Cells Induce Nitric Oxide-Dependent DNA Damage and p53 Pathway Activation in CD8⁺ T Cells.

ABSTRACT: Tumor-infiltrating myeloid-derived suppressor cells (MDSC) are associated with poor survival outcomes in many human cancers. MDSCs inhibit T cell-mediated tumor immunity in part because they strongly inhibit T-cell function. However, whether MDSCs inhibit early or later steps of T-cell activation is not well established. Here we show that MDSCs inhibited proliferation and induced apoptosis of CD8⁺ T cells even in the presence of dendritic cells (DC) presenting a high-affinity cognate peptide. This inhibitory effect was also observed with delayed addition of MDSCs to cocultures, consistent with functional data showing that T cells expressed multiple early activation markers even in the presence of MDSCs. Single-cell RNA-sequencing analysis of CD8⁺ T cells demonstrated

SUBMITTER: Cartwright ANR 

PROVIDER: S-EPMC8137551 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature