Interleukin-4 modulates type I interferon to augment antitumor immunity
- Author(s)
- Newnes, HV; Armitage, JD; Buzzai, AC; de Jong, E; Audsley, KM; Barnes, SA; Srinivasan, S; Serralha, M; Fear, VS; Guo, BB; Jones, ME; Forrest, ARR; Foley, B; Darcy, PK; Beavis, PA; Bosco, A; Waithman, J;
- Details
- Publication Year 2025-05-16,Volume 11,Issue #20,Page eadt3618
- Journal Title
- Science Advances
- Publication Type
- Research article
- 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 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.
- Publisher
- American Association for the Advancement of Science
- Keywords
- Animals; *Interferon Type I/metabolism/genetics/immunology; *Interleukin-4/metabolism/genetics/immunology; Mice; Tumor Microenvironment/immunology; *Melanoma, Experimental/immunology/pathology/therapy; Cell Line, Tumor; Signal Transduction; Mice, Inbred C57BL; Humans
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1126/sciadv.adt3618
- Open Access at Publisher's Site
https://doi.org/10.1126/sciadv.adt3618- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-06-03 03:44:05
Last Modified: 2025-06-03 03:44:24