Pathological perspectives on immune-related adverse events

Area of Science:

• Oncology
• Immunology
• Pathology

Background:

• Immune checkpoint inhibitors (ICIs) are increasingly used in cancer therapy, including combination regimens and neoadjuvant treatment.
• While ICIs improve outcomes for some patients, they also cause immune-related adverse events (irAEs), posing clinical challenges.
• The therapeutic benefits and detrimental side effects of ICIs are linked to the underlying mechanisms of immune activation.

Purpose of the Study:

• To explore the pathological basis of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs).
• To integrate clinicopathological observations across organ systems to enhance understanding and management of irAEs.
• To illustrate how tissue-based findings can inform the recognition and treatment of irAEs.

Main Methods:

• Review of clinical and pathological data related to immune checkpoint inhibitors (ICIs) and their associated immune-related adverse events (irAEs).
• Focus on representative and clinically relevant topics, analyzed from a pathological perspective.
• Integration of clinicopathological observations across multiple organ systems.

Main Results:

• Immune-related adverse events (irAEs) are closely associated with the mechanisms driving therapeutic immune activation by ICIs.
• Tissue-based findings provide insights into the development and manifestation of irAEs.
• A shared biological framework links the efficacy and toxicity of ICIs.

Conclusions:

• Understanding the pathological mechanisms of irAEs is crucial for managing ICI therapy.
• Clinicopathological integration aids in the recognition and management of irAEs.
• Considering benefits and disadvantages within the same biological framework is essential for optimizing ICI use.