For instance, up-regulated Tregs cells in the TME induce DNA damage in CD4(+) T and CD8(+) T cells and overexpress senescence-associated β-galactosidase (SA-β-Gal), promoting cell cycle progression and growth arrest in the G0/G1 phase, leading to T cells senescence and impaired tumour immunosuppressive capacities, which are co-regulated by MAPK and STAT1/STAT3 signaling pathways (226). The gene discussed is CD4; the disease is neoplasm.