Review of T Helper 2-Type Inflammatory Diseases Following Immune Checkpoint Inhibitor Treatment

Abstract

Immune checkpoints are mechanisms that allow cancer cells to evade immune surveillance and avoid destruction by the body’s immune system. Tumor cells exploit immune checkpoint proteins to inhibit T cell activation, thus enhancing their resistance to immune attacks. Immune checkpoint inhibitors, like nivolumab, work by reactivating these suppressed T cells to target cancer cells. However, this reactivation can disrupt immune balance and cause immune-related adverse events. This report presents a rare case of prurigo nodularis that developed six months after administering nivolumab for lung adenocarcinoma. While immune-related adverse events are commonly linked to T helper-1- or T helper-17-type inflammations, T helper-2-type inflammatory reactions, as observed in our case, are unusual. The PD-1–PD-L1 pathway is typically associated with T helper-1 and 17 responses, whereas the PD-1–PD-L2 pathway is linked to T helper-2 responses. Inhibition of PD-1 can enhance PD-L1 functions, potentially shifting the immune response towards T helper-1 and 17 types, but it may also influence T helper-2-type inflammation. This study reviews T helper-2-type inflammatory diseases emerging from immune checkpoint inhibitor treatment, highlighting the novelty of our findings.