CD4 and neoplasm: Preclinical studies suggested that sorafenib, a VEGFR-TKI, does not inhibit the effects of IL-21 on CD4+ or CD8+ T cell proliferation, NK cell activation, or antibody-dependent cellular cytotoxicity; also, the IL-21 and sorafenib combination led to improved tumor shrinkage and survival time as compared to either therapy alone in the murine RenCa model [29].