Radiotherapy enhances metastasis through immune suppression by inducing PD-L1 and MDSC in distal sites

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B1010
Abstract ID: 6066

Presenting Author:
Hua L Liang , Research Associate Professor at Univ. of Chicago

Abstract:

Radiotherapy (RT) results in molecular and cellular changes locally and systemically. The rare occurrence of the “abscopal” effect, in which tumors regress outside of the irradiation field, suggests the complexity of the interaction between the anti- and pro-tumor host responses. Consequently, dissecting these responses is critical for improving radiotherapy. We used a heterologous two-tumor model to study a simplified response to ionizing radiation (IR) in which adaptive concomitant immunity was eliminated, revealing the pro-tumor suppressive effects including systemic increases in myeloid-derived suppressor cells (MDSCs) and PD-L1 expression on myeloid cells. Type I interferon responsive cytokine CXCL10 could serve as a signal to promote distant metastasis. We report that local tumor irradiation increases the potential for metastatic dissemination through systemic induction of PD-L1 and recruitment of MDSCs in distal, non-irradiated tissue. Our results suggest that patients with absent or low PD-L1 levels might benefit from PD-1/PD-L1 blockade and should be tested for PD-L1 induction following initiation of RT.