CD4 and neoplasm: Radiotherapy has been reported to promote immunosuppressive tumor microenvironment by (1) increasing transcription of HIF 1 alpha which induces Treg proliferation, MDSC accumulation, and M2 polarization of TAMs and (2) activating latent TGF-beta in the tumor that polarizes TAMs into M2 phenotype and converting CD4+ T-cells into Tregs (Figure 2) [53, 54].