T cell-mediated mechanisms of immune-related adverse events induced by immune checkpoint inhibitors

Area of Science:

• Immunology
• Oncology
• Pathology

Background:

• Immune checkpoint inhibitors (ICIs) have transformed cancer therapy by blocking molecules like CTLA-4, PD-1, and PD-L1.
• Despite clinical benefits, ICIs can cause immune-mediated toxicities known as immune-related adverse events (irAEs).

Purpose of the Study:

• To review the critical role of T cell subsets in the pathogenesis of irAEs.
• To explore T cell subset dysregulation as a key pathological feature of irAEs.

Main Methods:

• Literature review synthesizing recent advances in T cell subset contributions to irAEs.
• Analysis of emerging evidence on T cell activity in irAE-affected tissues.

Main Results:

• Dysregulated T cell subset activity, including autoreactive T cell activation and Treg imbalance, is observed in irAEs.
• Helper T cell and memory T cell dysfunction are implicated in irAE pathogenesis.
• Aberrant T cell subset activity mirrors mechanisms seen in classic autoimmune diseases.

Conclusions:

• T cell subset dysregulation is a central pathological feature of irAEs.
• Understanding these T cell roles offers potential for T cell-targeted biomarkers and therapies.
• Future strategies aim to mitigate irAE toxicity while preserving antitumor immunity.