Additionally, tumor endothelial cells can release several hypoxia-related factors such as vascular endothelial growth factor A (VEGF-A), which induces the expression of programmed cell death protein 1 (PD-1), T-cell immunoglobulin mucin-3 (TIM-3), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on CD8 T cells, rendering them dysfunctional. This evidence concerns the gene HAVCR2 and neoplasm.