Radiotherapy (RT) can in some circumstances stimulate anti-tumor immune responses but just as effectively suppress them in others. Ludwig Chicago researchers led by Hua Laura Liang and Director Ralph Weichselbaum reported in a Clinical Cancer Research paper in May that immunosuppression induced by RT is systemic and can promote metastasis. The researchers implanted on each side of a mouse a tumor from a distinct source—so they’d induce distinct immune responses—and hit only one of them with radiation. This allowed them to specifically identify the immune effects of RT without having to worry about the confounding effects of shared anti-tumor immune responses. These studies showed that local irradiation elevates systemic levels of myeloid-derived suppressor cells, which inhibit immune responses, while simultaneously inducing the systemic expression of the immune checkpoint molecule PD-L1 on dendritic cells and other myeloid cells that are critical to anti-tumor immunity. These systemic effects aided metastasis from the untreated tumor to the lung. The phenomenon was accompanied by increased PD-L1 expression in the lung, which was dependent on elevated serum levels and signaling of a chemotaxis factor, CXCL10, that was produced predominantly by myeloid-derived suppressor cells. Targeting this axis, they showed, slowed tumor growth and metastasis in mice treated with RT, suggesting a therapeutic strategy for further evaluation.
Radiotherapy Enhances Metastasis Through Immune Suppression by Inducing PD-L1 and MDSC in Distal Sites
Clinical Cancer Research, 2024 May 01