Although CD137 signaling itself seems to be multifaceted in terms of immune response modulation, the contrasting immune responses found in tumor-challenged CD137−/− mice—i.e., enhanced NK- and CD8+ T-cell responses against tumors—need to be fully understood because agonistic anti-CD137 mAbs are being evaluated as antitumor therapeutics based on their positive effects on CD8+ T cells (125, 126). This evidence concerns the gene CD8A and neoplasm.