Radiation therapy regulates TCF-1 to maintain CD8+T cell stemness and promotes anti-tumor immunotherapy.

• High-dose radiation can improve mouse survival through regulating the T cells stemness in tumor micro-environment. • This paper is the first time proposed that radiation can enhance the expression of TCF-1 + T cells through cGAS/STING axis. • The study provides evidence for the rational combination of radiation and STING agonists. Radiotherapy is a very effective cancer treatment, mainly through inducing DNA damage of cancer cells. Meanwhile, there is evidence that irradiation can also mobilize tumor-specific immunity, and recent investigations demonstrate that the efficiency of local high-dose radiotherapy is attributable to the presence of CD8+T cells. Here, we observed that high-dose radiation remarkably increased the enrichment of stem cell-like CD8+T cells. Moreover, cGAS/STING signaling augmented stem cell-like CD8+T cells and T stem-like central memory CD8+T cells in a mice tumor model after radiation. These findings raise our understanding of stem cell-like CD8+T cells after radiation stimulation and improve radiation therapy by driving the cGAS/STING signaling pathway for cancer multimodality therapy. [ABSTRACT FROM AUTHOR]