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Area of Science:

  • Oncology
  • Immunology
  • Dermatology

Background:

  • Immune checkpoint blockade (ICB) has transformed cancer treatment, notably for melanoma and nonmelanoma skin cancers.
  • Immune-related adverse events (irAEs) limit ICB efficacy, with skin toxicities being the most frequent and rapid.
  • Skin irAEs present as various autoimmune manifestations, complicating treatment management.

Purpose of the Study:

  • To review the current understanding of ICB in skin cancer treatment.
  • To explore the pathogenesis, clinical presentation, and management of skin irAEs.
  • To identify knowledge gaps and propose future research directions, particularly in preclinical skin modeling.

Main Methods:

  • Literature review and synthesis of existing research on ICB, skin cancers, and irAEs.
  • Analysis of autoimmune manifestations in the skin related to ICB.
  • Discussion of predictive biomarkers and therapeutic strategies based on skin pathogenesis.

Main Results:

  • ICB is effective against skin cancers but frequently causes skin irAEs.
  • Skin irAEs encompass a spectrum of autoimmune conditions.
  • Current understanding of irAE pathophysiology, especially in the skin, remains incomplete.

Conclusions:

  • Decoupling ICB toxicity from efficacy requires a deeper understanding of irAE pathophysiology.
  • An interdisciplinary approach, integrating skin immunology and autoimmune pathogenesis, is essential.
  • Further development of preclinical skin models is needed to advance irAE research.