CSF-1R in Cancer: More than a Myeloid Cell Receptor

Simple Summary Several studies have highlighted the importance of the myeloid receptor CSF-1R in the context of tumors as a key player in the generation of an immunosuppressive microenvironment. Since recent research has demonstrated its expression also on the surface of cancer cells, the relevance of CSF-1R in this field has increased. Why might myeloid receptors be expressed by tumor cells? What advantages does CSF-1R expression provide to cancer cells? The aim of this review is to gather available data on CSF-1R expression in cancer cells to provide a new way to consider this receptor. Although previous works demonstrated the pro-tumoral role of CSF-1R in cancer cells in different tumor types, the precise mechanisms regulating its expression in cancer cells are still unknown and need further investigation in order to identify novel tumoral markers and the possible candidate for therapeutic intervention.Abstract Colony-stimulating factor 1 receptor (CFS-1R) is a myeloid receptor with a crucial role in monocyte survival and differentiation. Its overexpression is associated with aggressive tumors characterized by an immunosuppressive microenvironment and poor prognosis. CSF-1R ligands, IL-34 and M-CSF, are produced by many cells in the tumor microenvironment (TME), suggesting a key role for the receptor in the crosstalk between tumor, immune and stromal cells in the TME. Recently, CSF-1R expression was reported in the cell membrane of the cancer cells of different solid tumors, capturing the interest of various research groups interested in investigating the role of this receptor in non-myeloid cells. This review summarizes the current data available on the expression and activity of CSF-1R in different tumor types. Notably, CSF-1R+ cancer cells have been shown to produce CSF-1R ligands, indicating that CSF-1R signaling is positively regulated in an autocrine manner in cancer cells. Recent research demonstrated that CSF-1R signaling enhances cell transformation by supporting tumor cell proliferation, invasion, stemness and drug resistance. In addition, this review covers recent therapeutic strategies, including monoclonal antibodies and small-molecule inhibitors, targeting the CSF-1R and designed to block the pro-oncogenic role of CSF-1R in cancer cells.