Previously we found that VEGF can bind to its receptor VEGFR2 and regulate hypoxia-inducible factor-1α through PI3K/Akt and MAPK/ERK signaling pathways, leading to tumor cell proliferation, antiapoptosis, and radioresistance.[21] Kim et al[22] found that VEGF up-regulates the expression of thymocyte selection-associated high mobility group box gene (TOX) in CD8+ T cells in TME, initiates the TOX-mediated transition to an immune-depleted state, and up-regulates multiple checkpoint inhibitory receptors on T cells. The gene discussed is TOX; the disease is neoplasm.