Hou, Yuzhu and Yang, Kaiting and Wang, Liangliang and Wang, Jiaai and Huang, Xiaona and Piffko, Andras and Luo, Sean Z. and Yu, Xinshuang and Rao, Enyu and Martinez, Carlos and Bugno, Jason and Mack, Matthias and Vokes, Everett E. and Pitroda, Sean P. and Chmura, Steven J. and Weichselbaum, Ralph R. and Liang, Hua Laura (2024) Radiotherapy Enhances Metastasis Through Immune Suppression by Inducing PD-L1 and MDSC in Distal Sites. CLINICAL CANCER RESEARCH, 30 (9). pp. 1945-1958. ISSN 1078-0432, 1557-3265
Full text not available from this repository. (Request a copy)Abstract
Purpose: 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.Experimental Design: We used a heterologous two-tumor model in which adaptive concomitant immunity was eliminated.Results: 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.Conclusions: Blockade of PD-L1/CXCL10 axis or MDSC infiltration during irradiation can enhance abscopal tumor control and reduce metastasis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR MICROENVIRONMENT; ANTITUMOR IMMUNITY; IFN-GAMMA; RADIATION; IMMUNOTHERAPY; MECHANISMS; EXPRESSION; NIVOLUMAB; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Dec 2025 10:04 |
| Last Modified: | 17 Dec 2025 10:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65364 |
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