In view of the strongly diverging possibilities of targeting TNFR2 (activation or inhibition of TNFR2 signaling, destruction of TNFR2+ cells), which all showed promising results in preclinical models, a major challenge is certainly the question of on which basis or with which rationale cancer patients can be selected for a defined TNFR2 targeting strategy (TNFR2 blockade, TNFR2 engagement, ADCC) in clinical trials. This evidence concerns the gene TNFRSF1B and cancer.