CSF1 (colony stimulating factor 1) is a cytokine essential for the survival, proliferation, and differentiation of mononuclear phagocytes, particularly macrophages and monocytes. It also plays critical roles in osteoclast regulation and bone development, and is required for normal fertility. Beyond its classical hematopoietic functions, CSF1 regulates cell migration, cytoskeletal reorganization, and lipoprotein clearance. CSF1 signals through the CSF1 receptor (CSF1R) to modulate immune and inflammatory responses. In the tumor microenvironment, CSF1 drives macrophage polarization toward an alternatively activated (M2) phenotype that promotes immune evasion. In hepatocellular carcinoma, the PKCα/ZFP64/CSF1 axis mediates anti-PD1 resistance by shifting macrophages to an M2 phenotype 1. Similarly, in breast and endometrial cancers, tumor-associated macrophages produce CSF1 in an auto-regulatory loop that reinforces a tumor-permissive microenvironment 2. In esophageal squamous cell carcinoma, mutant p53 upregulates CSF1 expression through a BRD4-dependent mechanism that promotes epithelial-to-mesenchymal transition and lung metastasis 3. Clinically, CSF1/CSF1R-targeting agents show promise: pexidartinib (a CSF1R inhibitor) is FDA-approved for tenosynovial giant cell tumors 4, and lenvatinib or protein kinase inhibitors can restore anti-PD1 sensitivity in HCC by blocking the PKCα/ZFP64/CSF1 axis 1. BRD4 inhibitors suppress tumor-associated macrophage proliferation partly through CSF1 downregulation 5. These agents represent promising combination partners with immunotherapy and standard treatments.