Interleukin-4 modulates type I interferon to augment antitumor immunity
Menée à l'aide de lignées cellulaires et de modèles murins de mélanome, cette étude démontre que l'introduction d'interleukine IL-4 dans les tumeurs exprimant fortement l'interféron de type I et présentant une faible inflammation de type 2 accroît l'immunité antitumorale
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 tumor microenvironment, either through ectopic expression or in a preclinical adoptive T cell therapy model. Collectively, our findings highlight the IFN-I/IL-4 axis in promoting antitumor immunity, which could be harnessed to target and stratify solid tumors that are nonresponsive to frontline therapies. A therapeutic strategy that harnesses the IL-4/IFN-I axis to improve antitumor T cell immunity.
Science Advances , article en libre accès, 2025