Interleukin-4 modulates type I interferon to augment antitumor immunity.

ABSTRACT: Despite advances in immunotherapy, metastatic melanoma remains a considerable therapeutic challenge due to the complexity of the tumor microenvironment. Intratumoral type I interferon (IFN-I) has long been associated with improved clinical outcomes. However, several IFN-I subtypes can also paradoxically promote tumor growth in some contexts. We investigated this further by engineering murine B16 melanoma cells to overexpress various IFN-I subtypes, where a spectrum of outcomes was observed. Characterization of these tumors by RNA sequencing revealed a tumor immune phenotype, where potent IFN-I signaling concomitant with diminished type 2 inflammation failed to confer durable tumor control. T cell-mediated rejection of these tumors was restored by introducing interleukin-4 (IL-4) into the t

SUBMITTER: Newnes HV 

PROVIDER: S-EPMC12077506 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature