Finally, given the known relationship between angiogenesis and immunosuppression in the tumor microenvironment (21, 145), the potential effects of anti-angiogenic agents may be underestimated without also accounting for tumor expression of related biomarkers such as PD-1/PD-L1 and the effects VEGF-TKIs may have on these pathways, or accounting for combination therapy. The gene discussed is VEGFA; the disease is neoplasm.