CTLA4 and melanoma: Patients with severe toxicity (irAEs Grade≥3) are increased from 10.0% in the PD-1 inhibitor group to 31.0% in the CTLA-4 inhibitor group.193,194 Grade≥3 irAEs, including increased lipase and aminotransferase, are increased from 9.7 to 18.9% when combining PD-1 with LAG-3 inhibitors in advanced melanoma patients.51 Drug combination or multi-target combination is the main direction of improving the efficacy of ICB immunotherapy, but attention should be paid to controlling adverse reactions in the development of new targets for drug combination with a PD-1 inhibitor.