Tape Strip Profiling of Checkpoint Inhibitor–Associated Dermatitis Highlights Pan-T-Cell Activation: A Pilot Study

Camille M. Powers , Madeline Kim , Annie Chang , Benjamin D. Hu , Brandon R. Block , Austin J. Piontkowski , Jeremy Orloff , Jade N. Young , Yeriel D. Estrada , Digpal S. Gour , Emma Guttman-Yassky , Nicholas Gulati
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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, JAK3 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.
检查点抑制剂相关皮炎的条带分析强调泛t细胞激活:一项试点研究
免疫检查点抑制剂(ICIs)已成为治疗某些癌症的主要疗法。然而,它们通常与非肿瘤组织的不良反应有关。皮肤免疫相关不良事件是最普遍的毒性,但其潜在机制仍知之甚少。本初步研究采用微创胶带取样的方法研究了ici相关湿疹性皮炎和ici相关扁平苔藓的分子表型,并将这些情况与特应性皮炎患者和健康对照进行了比较。转录组学分析显示,在病变性ici相关的湿疹性皮炎和ici相关的扁平苔藓中,T辅助细胞1显著上调,超过了特应性皮炎中的失调。包括IL4R在内的辅助性T - 2相关标志物在两种ICI亚型中均升高,这与先前dupilumab对皮肤免疫相关不良事件疗效的临床报告一致。值得注意的是,JAK3调节仅在病变性ici相关的湿疹性皮炎中被观察到。病变性和非病变性ici相关的扁平苔藓表现出广泛的免疫失调,提示在看似未受影响的皮肤中可能存在早期炎症活动。这些发现强调了与ICI无关的皮肤免疫相关不良事件相比,不同的免疫途径改变,揭示了在不影响ICI疗效的情况下管理这些疾病的潜在治疗靶点。未来有必要在更大的队列中进行研究,以验证这些观察结果并评估针对皮肤免疫相关不良事件的靶向干预措施。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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