In YP subject treated with both anti-PD-(L)1 and anti-CTLA-4, 125 (4.0%) patients developed colitis, 49 (1.6%) developed hepatitis, 23 (0.7%) developed hypophysitis, 45 (1.4%) developed diabetes, implying an increased risk of irAEs with the combination treatment (Table 3, p<0.05). This evidence concerns the gene CTLA4 and hypophysitis.