During tumorigenesis, oncogenic pathways, genetic and epigenetic factors intrinsic to the tumor itself, as well as extrinsic factors in TME, such as cytokines IFN-γ, interleukin (IL)-6, and tumor necrosis factor (TNF), upregulate the expression of PD-1 ligands (L)1 (B7H1) and L2 (PD-L2) on tumor cells [153,154], leading to cancer immune escape [155]. Here, TNF is linked to neoplasm.