CD4 and neoplasm: Radiation, especially high single-fraction RT doses, can create a hypoxic TME, in which tumor cells produce CCL2, CCL5 and CXCL12 to recruit macrophages to create an immunosuppressive TME.1,92 Colony stimulating factor-1 (CSF-1), which is abundant in the hypoxic TME, contributes to the proliferation, differentiation and migration of TAMs by binding CSF-1R on TAMs.93 RT can drive the Th2 polarization of CD4+ T cells, causing them to express the cytokines mentioned above to promote M2 polarization.