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Low-Dose Radiation Improves the Tumor Immune Microenvironment through IFN Production: An In Vivo Study Using Murine Lung Cancer Model

Jigang Dong1,2, Xindi Li , Shasha2, Qi Ying2, Baosheng Li3

Background: Exposure to radiation prompts apoptosis within cancer cells, initiating ‘consume me’ signals including phosphatidylserine and calreticulin. This activation of dendritic cells paves the way for immune responses mediated by T and NKT cells, as well as the engulfment of cells by macrophages.

Objectives: In our study, we focused on the effects of low-dose radiation on Interferon (IFN) production, thereby enhancing immunogenic cell death in tumor cells.

Methods: In a study utilizing a murine lung cancer model, Lewis Lung Carcinoma (LLC) cells were administered to C57BL/6 mice. Following tumor development, these mice were segregated into cohorts. One cohort received a regimen of low-dose radiation therapy, while another was treated with CTLA-4 antibody injections.

Results: We found that low-dose radiation of 0.1 Gy promoted the production of IFN, and the contents of CXCL9, CXCL10 and CXCL11 in the tumor tissues were likewise significantly elevated after low-dose irradiation, which promoted the infiltration of CD8T cells in the tumor tissues, and ultimately inhibited the growth of the tumors in mice.

Conclusion: Low-dose radiation enhances immunogenic cell death in tumor cells by stimulating IFN production. These findings highlight the potential therapeutic significance of LDR in remodeling the tumor immune microenvironment, which warrants further exploration of its clinical applications in cancer therapy.