Researchers led by Ludwig Chicago Co-director Ralph Weichselbaum reported in a Nature publication in May that high doses of radiation aimed at a single tumor can accelerate the growth of existing metastases elsewhere in the body. The study, to which Ludwig Chicago’s András Piffkó, Kaiting Yang, Sean Pitroda and Hua Laura Liang contributed equally, analyzed samples from a clinical trial in which patients with various cancers received focused high-dose radiotherapy (stereotactic body radiotherapy, SBRT) combined with checkpoint blockade immunotherapy (pembrolizumab). Gene expression analysis revealed that SBRT induced the expression of the growth factor amphiregulin, and higher levels correlated with a size increase of preexisting metastatic sites. This effect was recapitulated in mouse models of metastatic lung and breast cancer. Elevated levels of amphiregulin were also found in the blood plasma of mice as well as patients enrolled in a trial evaluating SBRT and immunotherapy, and were associated with worse outcomes. Mechanistic experiments showed that amphiregulin reprograms EGFR-expressing myeloid cells into an immune-suppressive state and increases tumor expression of CD47, a “don’t-eat-me” signal that prevents immune cells from engulfing cancer cells. Combining radiotherapy with antibodies that block amphiregulin and CD47 significantly improved control of metastases in mice.
Radiation-induced amphiregulin drives tumour metastasis
Nature, 2025 May 14