In TME, some effector molecules, including interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α), secreted by tumor-infiltrating CD8+ T cells, are decreased, while some molecular markers on cancer cells, such as T cell immunoglobulin and mucin domain-containing 3 (TIM-3) and programmed death 1 (PD-1) are increased, indicating that infiltrating CD8+ T cells are in a state of exhaustion and cannot play a normal anti-tumor effect [97]. This evidence concerns the gene HAVCR2 and neoplasm.