Fig. 1

The specific mechanisms of SBRT combined with PD-1/PD-L1 inhibitors. The supportive modulatory mechanisms include upregulation of immunogenic cell surface markers such as ICAM-1, MHC-1 and Fas, induction of immunogenic cell death, release of tumor antigen and cytokines as IFN, TNFα, IL-1, IL-6, and so on, and enhanced homing of immune cells to tumors. Notably, the activated immune response can further act on distant nonirradiated metastases to appreciably inhibit metastases progression. Besides, SBRT can also induce immunosuppressive effects involving increased release of negative cytokines like TGFβ, accumulation of radioresistant suppressor cells, and upregulation of PD-L1 expression. The integration of PD-1/PD-L1 inhibitors to SBRT could not only enhance positive immunoregulation, but also significantly attenuate negative immune resistance, thus achieving potent anti-tumor immunity. Challenges exist to eliminate the remained suppressive effects