At present, several strategies have been used in previous studies to reduce toxicity: a CD137-based antibody engaged with other specific molecule which specifically brings CD137 agonism to the tumor tissue microenvironment (42), an antibody with Fc lacking trimeric CD137 constructs to avoid FcɣR binding-mediated liver toxicity (43), intratumoral injections of low doses of CD137 mAb (44), and dose reduction with a combination of other immune-modulating agents (45). This evidence concerns the gene TNFRSF9 and neoplasm.