Severe colitis after PD-1 blockade with nivolumab in advanced melanoma patients: potential role of Th1-dominant immune response in immune-related adverse events: two case reports

Nivolumab is an immune checkpoint inhibitor specific to the programmed death 1 (PD-1) receptor. Nivolumab has shown clinical responses in many malignancies. Although immune-related adverse events (irAEs) associated with nivolumab are largely tolerable, severe irAEs have occurred in some patients. However, the mechanisms underlying the development of irAEs are not fully clarified. We report 2 patients with metastatic melanoma who developed colitis, an irAEs caused by nivolumab. Both patients experienced colitis after nivolumab administration. Pathological examination of the colon showed robust infiltration of CD8+ cells and T-bet expressing CD4+ cells in both cases, indicating helper T cells (Th) 1 to be responsible for the dominant response. Additionally, we observed the serum C-reactive protein level (CRP) as well as interleukin-6 (IL-6) reflected the clinical course of irAEs clearly in the two cases. Our two cases suggested that the development of irAEs due to nivolumab is associated with Th1 dominant response. CRP as well as IL-6 was found to be a potential biomarker for irAEs. Our findings may help to understand the mechanisms underlying irAEs caused by nivolumab and manage irAEs in clinical practice.