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Updated: Sep 19, 2025
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Tape Strip Profiling of Checkpoint Inhibitor-Associated Dermatitis Highlights Pan-T-Cell Activation: A Pilot Study
Camille M Powers1, Madeline Kim1, Annie Chang1
1Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Abstract:
Immune checkpoint inhibitors (ICIs) have become mainstay therapy in the treatment of certain cancers. However, they are frequently associated with adverse effects in nontumor tissues. Cutaneous immune-related adverse events are the most prevalent toxicities, yet their underlying mechanisms remain poorly understood. This pilot study investigated the molecular phenotype of ICI-associated eczematous dermatitis and ICI-associated lichen planus using minimally invasive tape strip sampling to compare these conditions with patients with atopic dermatitis and healthy controls. Transcriptomic analysis revealed significant T helper 1 upregulation in lesional ICI-associated eczematous dermatitis and ICI-associated lichen planus, surpassing the dysregulation seen in atopic dermatitis. T helper 2-related markers, including IL4R, were elevated in both ICI subtypes, aligning with prior clinical reports of dupilumab efficacy for cutaneous immune-related adverse events. Notably, J AK 3 modulation was uniquely observed in lesional ICI-associated eczematous dermatitis. Lesional and nonlesional ICI-associated lichen planus demonstrated broad immune dysregulation, suggesting possible early inflammatory activity in seemingly unaffected skin. These findings highlight distinct immune pathway alterations in cutaneous immune-related adverse events compared with their ICI-independent counterparts, shedding light on potential therapeutic targets to manage these conditions without compromising ICI efficacy. Future studies in larger cohorts are warranted to validate these observations and evaluate targeted interventions for cutaneous immune-related adverse events.
Insights
Immune checkpoint inhibitor (ICI) skin toxicities show distinct molecular patterns compared to atopic dermatitis. This research identifies unique immune pathways in ICI-associated dermatitis and lichen planus, offering potential therapeutic targets.
Area of Science:
- Immunology
- Dermatology
- Oncology
Background:
- Immune checkpoint inhibitors (ICIs) are crucial cancer therapies but can cause non-tumor tissue adverse effects.
- Cutaneous immune-related adverse events (irAEs) are common ICI toxicities with unclear mechanisms.
- Understanding these skin reactions is vital for patient management without compromising anti-cancer treatment.
Purpose of the Study:
- To investigate the molecular phenotype of ICI-associated eczematous dermatitis and lichen planus.
- To compare these conditions with atopic dermatitis and healthy controls using transcriptomic analysis.
- To identify distinct immune pathways in cutaneous irAEs for potential therapeutic targeting.
Main Methods:
- Pilot study utilizing minimally invasive tape strip sampling.
- Transcriptomic analysis of lesional and nonlesional skin.
- Comparison between ICI-associated conditions, atopic dermatitis, and healthy controls.
Main Results:
- Significant T helper 1 upregulation observed in lesional ICI-associated eczematous dermatitis and lichen planus, exceeding that in atopic dermatitis.
- Elevated T helper 2 markers, including IL4R, noted in both ICI subtypes.
- Unique JAK3 modulation identified in lesional ICI-associated eczematous dermatitis.
- Broad immune dysregulation found in both lesional and nonlesional ICI-associated lichen planus.
Conclusions:
- Cutaneous irAEs exhibit distinct immune pathway alterations compared to ICI-independent dermatoses.
- Findings suggest potential early inflammation in nonlesional skin of ICI-associated lichen planus.
- Identified pathways may represent novel therapeutic targets for managing irAEs while preserving ICI efficacy.
