CTLA4 and neoplasm: Within the tumor microenvironment, tumor cells can negatively impact the activity, proliferation, and viability of T and NK cells through various mechanisms such as nutrient depletion, pH reduction, hypoxia, metabolites, cytokines (e.g., lactic acid, kynurenines, IL-10, TGF-β, PGE2, and TNF-α), and modulation of surface molecule expression (e.g., CTLA-4, PD-L1, and reduced expression of costimulatory molecules) [12,26].