The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas

Macrophages accumulate with glioblastoma multiforme (GBM) progression and can be targeted via inhibition of colony-stimulating factor-1 receptor (CSF-1R) to regress high-grade tumors in animal models of this cancer. However, whether and how resistance emerges in response to sustained CSF-1R blockade is unknown. We show that although overall survival is significantly prolonged, tumors recur in >50% of mice. Gliomas reestablish sensitivity to CSF-1R inhibition upon transplantation, indicating that resistance is tumor microenvironment-driven. Phosphatidylinositol 3-kinase (PI3K) pathway activity was elevated in recurrent GBM, driven by macrophage-derived insulin-like growth factor-1 (IGF-1) and tumor cell IGF-1…

• AB
  American Brain Tumor Association
• LI
  Ludwig Institute for Cancer Research
• CI
  Canadian Institutes of Health Research
• NC
  National Cancer Institute

  Awards: F31CA167863, R01CA148967, P30 CA008748