The engagement of PD-1 by its ligands, PD-L1 and PD-L2, induces tumor immune escape and down-regulation of tumor-infiltrating lymphocytes (TILs) by different mechanisms such as: inhibiting T cell proliferation and induction of their apoptosis, reducing the inflammatory cytokines as IFN-γ, IL-2, TNF-α, inhibiting granular enzyme and perforin production by cytotoxic T lymphocytes (CTLs), and increasing metastasis and penetration of tumor cells (12–14). The gene discussed is TNF; the disease is neoplasm.