Reduced CSF1R expression in myeloid cells has limited impact on chronic lymphocytic leukemia progression

Abstract

Targeting the colony-stimulating factor 1 receptor (CSF1R) to remove tumor-associated macrophages is being explored as cancer therapy. This strategy may be relevant for chronic lymphocytic leukemia (CLL), which strongly depends on support from myeloid cells. However, it is unclear how CSF1R expression affects the CLL microenvironment and leukemic progression. To examine this question, we created CLL mice with Csf1r haploinsufficiency to investigate changes in myeloid cells, Csf1r expression, and leukemia progression. Reducing Csf1r expression on circulating monocytes did not change the overall numbers of monocytes or macrophages in blood and lymphoid tissues. Mice with lower Csf1r levels had less leukemia during early disease, but this effect faded with disease progression, and their overall survival was similar to controls. Furthermore, reduced Csf1r expression on macrophages did not affect the survival or migration of patient-derived CLL cells. In summary, our results show that while the CSF1R pathway is important for maintaining the myeloid cells that support CLL, simply reducing CSF1R expression has only a limited effect on disease progression. Attempts to target the CSF1R for leukemic therapy might benefit from a stronger depletion of macrophages or the combination with other agents.