Immune Checkpoint Inhibitor-Associated Cutaneous Adverse Events: Mechanisms of Occurrence

Area of Science:

• Oncology
• Dermatology
• Immunology

Background:

• Immunotherapy using immune checkpoint inhibitors (ICIs) is a vital cancer treatment alternative to chemotherapy for various neoplasms.
• ICIs target pathways to destroy cancer cells, proving effective in highly immune-infiltrated tumors.
• However, a significant proportion of patients develop cutaneous adverse effects during and after ICI therapy.

Purpose of the Study:

• To elucidate the mechanisms underlying the occurrence of cutaneous adverse effects following treatment with ICIs.
• To detail the common and severe skin reactions associated with ICI therapy.
• To provide insight into the T-cell mediated pathways driving these dermatological side effects.

Main Methods:

• Review of literature on immunotherapy-related adverse events (irAEs).
• Analysis of the molecular mechanisms of action for anti-PD-1, anti-CTLA-4, and anti-PD-L1 agents.
• Categorization of ICI-associated cutaneous adverse effects, including inflammatory and bullous dermatoses.

Main Results:

• ICI-associated cutaneous disorders are the most prevalent side effects of anti-PD-1, anti-CTLA-4, and anti-PD-L1 therapies.
• Common effects include inflammatory and bullous dermatoses, rash, and inflammatory dermatitis.
• Severe reactions encompass erythema multiforme, lichenoid, eczematous, psoriasiform, and morbilliform lesions, and palmoplantar erythrodysesthesia.
• These effects stem from the activation of cytotoxic CD4+/CD8+ T cells mediated by ICIs.

Conclusions:

• Cutaneous adverse effects are a common consequence of modern cancer immunotherapy with ICIs.
• Understanding the T-cell activation mechanisms is crucial for managing these dermatological side effects.
• Further research into managing irAEs can improve patient tolerance and treatment outcomes.