Dual checkpoint blockade with nivo-ipi avoids chemotherapy-related systemic toxicities (e.g., myelosuppression, gastrointestinal reactions, hepatic and renal injury), which may underlie its lower probability of grade ≥3 trAEs; however, concomitant PD-1 and CTLA-4 inhibition intensifies effector T-cell activation and impairs Treg function, further eroding self-tolerance and increasing the frequency and severity of irAEs such as rash and hypothyroidism (29). This evidence concerns the gene CTLA4 and hypothyroidism.