Recent studies have provided increasing evidence that co-stimulatory signals transmitted via a subset of molecules belonging to the TNFR superfamily, which are critical for the development of protective immunity, as well as for the treatment of inflammatory and cancer immunotherapy and these molecules include OX40 (TNFRSF4), 4-1BB (TNFRSF9), CD27, DR3 (TNFRSF25), CD30 (TNFRSF8), GITR (TNFRSF18), TNFR2 (TNFRSF1B), and HVEM (TNFRSF14), which is possible to enhance the effectiveness of immunotherapeutic treatments for cancer [105]. This evidence concerns the gene TNFRSF25 and cancer.