Low-dose radiotherapy encourages the generation of IFN and improves the tumor immune microenvironment

Abstract

Abstract Background Radiation-induced apoptosis in tumor cells triggers signals such as phosphatidylserine and calreticulin to attract and activate dendritic cells, leading to T and NKT cell-based immune responses and macrophage phagocytosis. Objectives This study explored the potential of low-measure radiation to stimulate interferon (IFN) production, thereby enhancing immunogenic cell death in tumor cells. Methods Using a murine Lewis lung carcinoma model, mice underwent LDR (0.1 Gy every other day for five cycles), CTLA-4 treatment, or their combination. Flow cytometry, ELISA, immunohistochemistry, and RNA sequencing assessed immune cell infiltration, cytokine levels, and tumor growth dynamics. The role of IRF7 and IFN in LDR-mediated immune modulation was explored genetically and at the protein level. Results LDR enhanced IFN-α production, upregulated chemokines, and increased CD8 T cell infiltration in tumors. IRF7 emerged as a key mediator, with LDR promoting its expression, nuclear translocation, and heightened IFN production. Combining LDR with CTLA-4 synergistically suppressed tumor growth, increased CD8 T cell infiltration, and elevated IFN-γ levels. Conclusion LDR, through IRF7-mediated IFN induction, reshapes the tumor microenvironment, fostering anti-tumor immune responses. The synergy of LDR and CTLA-4 presents a potential strategy to address current cancer therapy challenges. This study contributes insights into LDR's immunomodulatory role, suggesting broader applications beyond cancer treatment.