CD137 (4-1BB) is expressed on innate (DC and NK) and adaptive (T) immune cells as a member of the co-stimulating tumor necrosis factor (TNF) receptor superfamily (TNFRSF), which determines the degree of T cell activation, function, and survival, coupled with its unique ability to enhance anti-tumor and improve autoimmune responses, making it a promising target for clinical cancer immunotherapy [164]. This evidence concerns the gene TNFRSF9 and cancer.