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Published on: February 25, 2020
Cutaneous immune-related adverse events to immune checkpoint inhibitors: from underlying immunological mechanisms to
Ting Cao1, Xuyang Zhou1, Xingbiao Wu1
1Allergic Dermatoses Clinical Center, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
Abstract:
The development of immune checkpoint inhibitors (ICIs) has dramatically altered the landscape of therapy for multiple malignancies, including urothelial carcinoma, non-small cell lung cancer, melanoma and gastric cancer. As part of their anti-tumor properties, ICIs can enhance susceptibility to inflammatory side effects known as immune-related adverse events (irAEs), in which the skin is one of the most commonly and rapidly affected organs. Although numerous questions still remain unanswered, multi-omics technologies have shed light into immunological mechanisms, as well as the correlation between ICI-induced activation of immune systems and the incidence of cirAE (cutaneous irAEs). Therefore, we reviewed integrated biological layers of omics studies combined with clinical data for the prediction biomarkers of cirAEs based on skin pathogenesis. Here, we provide an overview of a spectrum of dermatological irAEs, discuss the pathogenesis of this "off-tumor toxicity" during ICI treatment, and summarize recently investigated biomarkers that may have predictive value for cirAEs via multi-omics approach. Finally, we demonstrate the prognostic significance of cirAEs for immune checkpoint blockades.
Insights
Immune checkpoint inhibitors (ICIs) can cause skin side effects called cutaneous immune-related adverse events (cirAEs). Multi-omics studies identify biomarkers to predict and understand these toxicities.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment across various malignancies.
- A significant challenge with ICIs is the occurrence of immune-related adverse events (irAEs), particularly cutaneous irAEs (cirAEs).
Purpose of the Study:
- To review the spectrum and pathogenesis of dermatological irAEs induced by ICIs.
- To summarize multi-omics biomarkers for predicting cirAEs.
- To explore the prognostic significance of cirAEs in patients receiving ICI therapy.
Main Methods:
- Literature review integrating multi-omics data (genomics, transcriptomics, proteomics, etc.) with clinical information.
- Analysis of immunological mechanisms underlying ICI-induced skin toxicities.
- Synthesis of current research on predictive biomarkers for cirAEs.
Main Results:
- Skin is a frequently affected organ in ICI-related irAEs.
- Multi-omics approaches are revealing insights into the immune system's role in cirAE development.
- Several potential biomarkers are emerging from integrated omics and clinical data for predicting cirAEs.
Conclusions:
- Understanding the pathogenesis of cirAEs is crucial for managing ICI therapy.
- Multi-omics studies offer promising avenues for identifying predictive biomarkers of cirAEs.
- CirAEs may hold prognostic value for the efficacy of immune checkpoint blockade treatments.
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