Radiotherapy Enhances Metastasis Through Immune Suppression by inducing PD-L1 and MDSC in distal sites

Radiotherapy (RT) is a widely employed anti-cancer treatment. Emerging evidence suggests that RT can elicit both tumor-inhibiting and tumor-promoting immune effects. This study is to investigate immune suppressive factors of radiotherapy.We used a heterologous two-tumor model in which adaptive concomitant immunity was eliminated.Through analysis of PD-L1 expression and MDSC frequencies using patient PBMC and murine two-tumor and metastasis model, we report that local irradiation can induce a systemic increase in MDSCs, as well as PD-L1 expression on DCs and myeloid cells, and thereby increase the potential for metastatic dissemination in distal, non-irradiated tissue. In a mouse model using two distinct tumors, we found that PD-L1 induction by ionizing radiation (IR) was dependent on elevated chemokine CXCL10 signaling. Inhibiting PD-L1 or MDSCs can potentially abrogate RT-induced metastasis and improve clinical outcomes for patients receiving RT.Blockade of PD-L1/CXCL10 axis or MDSC infiltration during radiation can enhance abscopal tumor control and reduce metastasis.