One potential explanation for this is that the tumor microenvironment provides inhibitory signals, such as PD-1 and CTLA-4, which prevent these cells from progressing through the division cycle despite their metabolic capabilities, resulting in a state of ‘functional entrapment.’ Alternatively, these metabolic alterations may represent an adaptive response of T cells to microenvironmental stresses, including hypoxia and nutrient deprivation [83,86]. The gene discussed is CTLA4; the disease is neoplasm.