Ludwig Lausanne’s Johanna Joyce and colleagues reported in Science Translational Medicine in July how radiotherapy affects immune cells known as macrophages in glioblastoma (GBM) tumors and showed how these cells might be reprogrammed to control GBM recurrence. Gliomas harbor both the brain’s resident macrophages, microglia (MG), and recruited monocyte-derived macrophages (MDM), which ordinarily patrol the body. Gliomas can push both into an alternative activation state—the M2-like phenotype—in which they support tumor growth. The researchers found both MG and MDMs flood into GBM tumors in mice following an initial course of radiotherapy, and their M2-like phenotype is further exacerbated. When the gliomas recur, it is MDMs that predominate within them. Johanna’s lab has previously reported that CSF-1R inhibitors can reverse the M2-like phenotype. In the current study, they used one of these drugs to show that a daily regimen of CSF-1R inhibition following radiotherapy effectively reprogrammed TAMs and extended survival through the full six months of the study for 95% of the mice, compared to a survival increase of nearly three weeks observed with radiotherapy alone. By contrast, short-term CSF-1R inhibition (for 12 days) plus radiation resulted in only a transient improvement, which may have implications for the evaluation and dosing regimens of such drugs in clinical trials.
This article appeared in the December 2020 issue of Ludwig Link. Click here to download a PDF (1 MB).