The involvement of TRAF3 in cancer pathogenesis has been extensively studied (reviewed in [46]) and, while most evidence identifies TRAF3 as a tumor suppressor, as found in an HPV-positive head and neck cancer cohort [47], TRAF3 was recently found to have an immune-suppressive role and to limit the response to immune checkpoint blockade in melanoma [35]. The gene discussed is TRAF3; the disease is head and neck cancer.