Pathological perspectives on immune-related adverse events

Over the past decade, immune checkpoint inhibitors (ICIs) have moved from the research setting into routine clinical practice. Their use has expanded from single-agent therapy to combination regimens with cytotoxic chemotherapy, targeted agents, and radiotherapy, and more recently being incorporated into neoadjuvant treatment. Although ICIs have improved the outcomes of a subset of patients, this progress has been accompanied by the occurrence of immune-related adverse events (irAEs), which represent an important challenge in daily clinical care. Ongoing research continues to pursue more effective and durable antitumor immune responses. At the same time, enhanced immune activation is associated with an increased risk of unintended tissue injury, suggesting that irAEs are closely linked to the mechanisms underlying therapeutic immune activation. Therefore, the benefits and disadvantages of ICIs should be considered within the same biological framework. This review does not aim to provide a comprehensive catalog of irAEs; instead, we highlight several representative and clinically relevant topics and discuss them from a pathological perspective. By integrating clinicopathological observations across organ systems, we seek to illustrate how tissue-based findings can contribute to the understanding, recognition, and management of irAEs.