These converging findings from multiple studies highlight the trade-off between efficacy and toxicity, where CTLA-4 inhibition undermines self-tolerance more profoundly than PD-1/PD-L1 blockade, elevating the likelihood of autoimmune-like conditions in joints (arthritis) and mucocutaneous regions (oral sores), as evidenced by case reports of severe irAEs like grade 4 mucositis and esophagitis associated with pembrolizumab [44, 45, 47]. This evidence concerns the gene CD274 and arthritic joint disease.