Immune checkpoint inhibitors and diabetes: Mechanisms and predictors

Area of Science:

• Immunology
• Oncology
• Endocrinology

Background:

• Immune checkpoint inhibitors (ICIs) revolutionized cancer immunotherapy.
• Adverse effects, including autoimmune diseases like diabetes mellitus, are associated with ICIs.
• Programmed cell death 1 (PD-1) and Programmed death ligand-1 (PD-L1) inhibitors are key therapeutic agents.

Purpose of the Study:

• To elucidate the mechanisms by which PD-1/PD-L1 inhibitors induce diabetes.
• To review the role of PD-1/PD-L1 in autoimmunity and diabetes pathogenesis.
• To identify strategies for managing or preventing ICI-induced diabetes.

Main Methods:

• Review of existing literature on PD-1/PD-L1 inhibitors and diabetes.
• Analysis of case reports and mechanistic studies.
• Examination of mouse models and genetic studies related to PD-1/PD-L1 and diabetes.
• Synthesis of data on patient risk stratification for autoimmune adverse events.

Main Results:

• PD-1/PD-L1 inhibitors can disrupt immune homeostasis, leading to autoimmune diabetes.
• Specific genetic variations in PD-1/PD-L1 may influence diabetes risk.
• Mouse models provide insights into the immunological pathways involved.
• Studies are emerging to identify at-risk patient populations.

Conclusions:

• Understanding the mechanisms of ICI-induced diabetes is crucial for patient safety.
• Further research is needed to develop predictive biomarkers and targeted interventions.
• Balancing antitumor efficacy with the management of autoimmune side effects remains a key challenge.