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CSF1R pathway expressed on an inactive T cell and tumor-associated macrophage diagram

Colony-stimulating factor 1 receptor (CSF1R) regulates macrophage differentiation and function and stimulates the development of tumor associated macrophages (TAMs). Inhibition of CSF1R may deplete TAMs and boost antitumor immunity.

  • CSF1R is a cell-surface receptor expressed by macrophages and other cells of the myeloid lineage1
    • CSF1 is a ligand for CSF1R2
    • IL-34 is another ligand for CSF1R and it is implicated in microglia regulation in the central nervous system3
  • The CSF1/CSF1R pathway is a dominant regulator of macrophage differentiation and function2
  • In preclinical studies, CSF1R blockade, depriving CSF1 of its target receptor, resulted in TAM depletion and improved T-cell responses7,8
  • In addition, the blockade of CSF1R in combination with other checkpoint pathways may improve T-cell function and enhance antitumor activity5,7,9
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How does CSF1R stimulate immunosuppression?

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1. Stanley ER, Chitu V. CSF-1 receptor signaling in myeloid cells. Cold Spring Harb Perspect Biol. 2014;6(6):a021857. doi:10.1101/cshperspect.a021857. 2. Richardsen E, Uglehus RD, Johnsen SH, Busund LT. Macrophage-colony stimulating factor (CSF1) predicts breast cancer progression and mortality. Anticancer Res. 2015;35(2):865-874. 3. Nandi S, Gokhan S, Dai X-M, et al. The CSF-1 receptor ligands IL-34 and CSF-1 exhibit distinct developmental brain expression patterns and regulate neural progenitor cell maintenance and maturation. Dev Biol. 2012;367(2):100-113. 4. Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity. 2014;41(1):49-61. 5. Zhu Y, Knolhoff BL, Meyer MA, et al. CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res. 2014;74(18):5057-5069. 6. Yang L, Wu Q, Xu L, et al. Increased expression of colony stimulating factor-1 is a predictor of poor prognosis in patients with clear-cell renal cell carcinoma. BMC Cancer. 2015. doi:10.1186/s12885-015-1076-5. 7. Ries CH, Cannarile MA, Hoves S, et al. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell. 2014;25(6):846-859. 8. Mitchem JB, Brennan DJ, Knolhoff BL, et al. Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses. Cancer Res. 2012;73(3):1128-1141. 9. Neubert NJ, Schmittnaegel M, Bordry N, Nassiri S, Wald N, Martignier C, Tillé L, Homicsko K, Damsky W, Maby-El Hajjami H, Klaman I. T cell–induced CSF1 promotes melanoma resistance to PD1 blockade. Science translational medicine. 2018;10(436):eaan3311.