When tumor cells expressing PD-L2 bind to PD-1 (CD279) on T cells for synergistic signaling, it induces dephosphorylation of binding protein tyrosine phosphatases and affects downstream signaling pathways such as PI3K/Akt, Ras/ERK, PLCγ, and VAV, leading to immunosuppression and cancer progression by inhibiting T cell activation, proliferation, survival, and cytolytic functions in the tumor microenvironment (Figure 1E) (11). The gene discussed is PDCD1LG2; the disease is neoplasm.