CD4 and neoplasm: The tumor microenvironment is a hostile environment for effector cells due to its high acidity (pH 6.0–6.9), high lactate levels, hypoxia, essential amino acids scarcity, extracellular matrix remodeling, abnormal vasculature, as well as the presence of immunosuppressive proteins and cytokines (such as FasL, IL-10, TGF-β) secreted by the CD4+ FOXP3+ cells, myeloid-derived suppressor cells, and M2 macrophages [35,36].