T cell exhaustion is triggered by the following four factors in the TME: 1) long-term antigen stimulation and high expression of co-inhibitory receptors/immune checkpoints; 2) soluble cytokines (type I interferon, IL-2, IL-10, and transforming growth factor-β (TGF-β)) in the TME; 3) recruitment of immunosuppressive cells: regulatory T cells (Tregs), Myeloid-Derived Suppressor Cell (MDSC), and tumor-associated macrophages (TAMs); 4) and the lack of oxygen and nutrients in the TME (6). The gene discussed is IL2; the disease is neoplasm.