The combination of other therapeutics with ICIS is able to modify the immune microenvironment of the tumor, up-regulating T cells with effector functions, and decreasing the immunosuppressive cells expression, and so changing a cold tumor into a hot one The combination of ICIs with anti-Vascular Endothelial Growth Factor (VEGF) therapy is a major approach under investigation for HCC patients using the immunomodulatory effects of an anti-VEGF drug as a means of decreasing CD4+ regulatory T-Lymphocytes and MDSCs as well as the activation and differentiation of DCs [43,44]. Here, CD4 is linked to neoplasm.