IAP Antagonists Enhance Cytokine Production from Mouse and Human iNKT Cells.

ABSTRACT: Inhibitor of apoptosis protein (IAP) antagonists are in clinical trials for a variety of cancers, and mouse models show synergism between IAP antagonists and anti-PD-1 immunotherapy. Although IAP antagonists affect the intrinsic signaling of tumor cells, their most pronounced effects are on immune cells and the generation of antitumor immunity. Here, we examined the effects of IAP antagonism on T-cell development using mouse fetal thymic organ culture and observed a selective loss of iNKT cells, an effector cell type of potential importance for cancer immunotherapy. Thymic iNKT-cell development probably failed due to increased strength of TCR signal leading to negative selection, given that mature iNKT cells treated with IAP antagonists were not depleted, but had enhanced cytokine producti

SUBMITTER: Clancy-Thompson E 

PROVIDER: S-EPMC5754232 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature