Melanoma-intrinsic NR2F6 activity regulates antitumor immunity.

ABSTRACT: Nuclear receptors (NRs) are implicated in the regulation of tumors and immune cells. We identify a tumor-intrinsic function of the orphan NR, NR2F6, regulating antitumor immunity. NR2F6 was selected from 48 candidate NRs based on an expression pattern in melanoma patient specimens (i.e., IFN-γ signature) associated with positive responses to immunotherapy and favorable patient outcomes. Correspondingly, genetic ablation of NR2F6 in a mouse melanoma model conferred a more effective response to PD-1 therapy. NR2F6 loss in B16F10 and YUMM1.7 melanoma cells attenuated tumor development in immune-competent but not -incompetent mice via the increased abundance of effector and progenitor-exhausted CD8⁺ T cells. Inhibition of NACC1 and FKBP10, identified as NR2F6 effectors, phenocopied

SUBMITTER: Kim H 

PROVIDER: S-EPMC10321753 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature