MTORC2 inhibition reduces tumor burden via STAT1 activation and enhanced response to anti-PD-L1 therapy.

ABSTRACT: Although melanoma treatment has progressed considerably in recent years, increasing patient response rates remains a significant challenge. The interferon pathway is known to promote immune recognition, but its sustained activation can contribute to adaptive immune exhaustion. In this study, we demonstrate that myeloid-specific deletion of Rictor in a mouse melanoma model enhances STAT1 signaling while reducing PD-L1 expression. Furthermore, IFN-γ-activated macrophages inhibited melanoma growth in a human skin organoid model. Notably, in vivo inhibition of AKT, in conjunction with anti-PD-L1 therapy, suppressed tumor progression. Mechanistically, we identified IFN-γ-mediated downregulation of IGF-1 as a key event during inflammation, and showed that supplementation with recombinant IGF-1 d

SUBMITTER: Gschwendtner A 

PROVIDER: S-EPMC12749672 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature