Work

Strong pro-tumoral immune effect mediated by a prominent interferon-stimulated gene 2695

Year: 2025

Type: article

Abstract: Description Interferons (IFNs) are cytokines well-known for their anti-tumoral effects in humans and mice. Deletion of their receptors in murine models inhibits immunosurveillance and promotes tumor growth. Local and systemic effects of IFNs are mediated by induction of hundreds of IFN-stimulated genes (ISGs) in target cells. Recently, we discovered that the deletion of a prominent ISG in mice resulted in complete tumor elimination using different orthotopic (melanoma, breast, pancreas) and heterotopic (subcutaneous) syngeneic tumor models. Bone marrow transfer, antibody-mediated depletion, and T-cell transfer data indicated that tumor regression in KO mice is bone-marrow derived but not dominant and T cell-mediated but not T cell-intrinsic. Immuno-phenotyping of lymphoid organs and tumors in active regression showed no apparent differences between KO animals and littermate controls but imaging analysis revealed distinct patterns of immune cell infiltration in tumors. Furthermore, KO mice are phenotypically and immunologically indistinguishable to littermates and KO mice that cleared tumor show no signs of autoimmunity. The Cancer Genome Atlas data indicated that expression of this ISG inversely correlates with patient survival in poor-prognosis cancer types (esophageal, pancreas, glioma). Taken together, we describe a strong pro-tumoral immune effect mediated by an ISG, suggesting that regulation of tumor immunity by IFNs might be more complex than previously anticipated. Funding Sources This work was supported by grants R01AI40646 and R35CA231620 from the U.S. National Institutes of Health (DRG) and ALSAC (American Lebanese Syrian Associated Charities). Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.584