In vitro studies have revealed that the increased levels of extracellular lactate and H+ in the tumor microenvironment can hamper proliferation, survival, cytotoxicity, and cytokine production in mouse and human CD8+ T cells, the fundamental players in eradicating tumor cells through triggering the signals from V-domain immunoglobulin suppressor of T-cell activation, an acidic pH-selective ligand for P-selectin glycoprotein ligand-1[60]. The gene discussed is SELPLG; the disease is neoplasm.