SMAC mimetics inhibit human T cell proliferation and fail to augment type 1 cytokine responses.

ABSTRACT: Second mitochondria-derived activator of caspases (SMAC) mimetics are small molecule drugs that mimic the activity of the endogenous SMAC protein. SMAC and SMAC mimetics antagonize inhibitors of apoptosis proteins (IAPs), thereby sensitizing cells to apoptosis. As such, SMAC mimetics are being tested in numerous clinical trials for cancer. In addition to their direct anti-cancer effect, it has been suggested that SMAC mimetics may activate T cells, thereby promoting anti-tumor immunity. Here, we tested the effect of three clinically relevant SMAC mimetics on activation of primary human T cells. As previously reported, SMAC mimetics killed tumor cells and activated non-canonical NF-κB in T cells at clinically relevant doses. Surprisingly, none of the SMAC mimetics augmented T cell responses

SUBMITTER: Burton AM 

PROVIDER: S-EPMC10319349 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature