Metformin can downregulate the ratio of TCM/TEM by inhibiting the apoptosis of TEM cells, and inducing the transformation of immune-depleted TCM to activated TEM with anti-tumor effects that increase TNF-α, IL-2, and IFN-γ secretion and thereby inhibit immune depletion of CD8+TILs caused by continuous tumor antigen stimulation, enhance local infiltrating CD8+TILs both in number and activity [27]. This evidence concerns the gene TNF and neoplasm.