journal contribution
posted on 2024-05-01, 07:20 authored by Yuzhu Hou, Kaiting Yang, Liangliang Wang, Jiaai Wang, Xiaona Huang, András Piffkó, Sean Z. Luo, Xinshuang Yu, Enyu Rao, Carlos Martinez, Jason Bugno, Matthias Mack, Everett E. Vokes, Sean P. Pitroda, Steven J. Chmura, Ralph R. Weichselbaum, Hua Laura Liang Supplementary figure 4. Multiplex Cytokine assay of local tumor, distal tumor, lung, and serum
of mice treated as indicated
Funding
National Cancer Institute (NCI)
United States Department of Health and Human Services
Find out more...Ludwig Cancer Research Foundation
National Natural Science Foundation of China (NSFC)
Clinical Therapeutics Training Grant
German Research Foundation Walter Benjamin scholarship
History
ARTICLE ABSTRACT
Radiotherapy (RT) is a widely employed anticancer treatment. Emerging evidence suggests that RT can elicit both tumor-inhibiting and tumor-promoting immune effects. The purpose of 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 myeloid-derived suppressor cells (MDSC) frequencies using patient peripheral blood mononuclear cells and murine two-tumor and metastasis models, we report that local irradiation can induce a systemic increase in MDSC, as well as PD-L1 expression on dendritic cells and myeloid cells, and thereby increase the potential for metastatic dissemination in distal, nonirradiated tissue. In a mouse model using two distinct tumors, we found that PD-L1 induction by ionizing radiation was dependent on elevated chemokine CXCL10 signaling. Inhibiting PD-L1 or MDSC can potentially abrogate RT-induced metastasis and improve clinical outcomes for patients receiving RT.
Blockade of PD-L1/CXCL10 axis or MDSC infiltration during irradiation can enhance abscopal tumor control and reduce metastasis.
