Furthermore, recent data in different types of tumors suggest that self-Ag released by dying cancer cells in the TME are recognized by Tregs, inducing their activation into effector Tregs expressing higher levels of activation markers (CTLA-4, TIGIT, TIM-3, ICOS, OX40, 4-1BB and CD39) and presenting a highly proliferative state, compared with Tregs in the peripheral blood or healthy tissues [13,14]. This evidence concerns the gene ICOS and cancer.