Azin Marjan, Farokh Parisa, McGarry Alexander, Leung Bonnie W, Roster Kathleen, Rashdan Hannah, Rajeh Ahmad, Khattab Sara, Stephens Michael R, Thang Christopher Jayee, Fisher David E, Nazarian Rosalynn M, Chen Steven T, Semenov Yevgeniy R, Demehri Shadmehr
Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
J Am Acad Dermatol. 2025 Aug 8. doi: 10.1016/j.jaad.2025.08.008.
Cutaneous immune-related adverse events (cirAEs) induced by immune checkpoint inhibitor (ICI) therapy share clinical features with spontaneous inflammatory dermatoses. However, the exact immunopathogenesis of cirAEs remains unclear.
To investigate the inflammation that mediates the most common cirAEs, lichenoid eruption (LE) and eczematous eruption (EE).
In a prospective cohort study, participants with cancer on ICI therapy with any clinically visible cirAEs were enrolled. T helper-1 (Th1) and Th2 cell responses in cirAEs were compared to spontaneous lichenoid dermatitis and eczematous dermatitis.
Among 88 cirAE biopsies collected, LE (35.22%) and EE (31.81%) accounted for most cases. In contrast to lichenoid dermatitis, we found that the CD4/CD8 T-cells and Th2/Th1 ratios were increased in ICI-induced LE, similar to EE. Importantly, we identified several cirAEs displaying a combination of LE and EE on pathology.
Only the most common types of cirAEs were evaluated, and Th17 cells were not analyzed.
Our findings indicate that LE and EE may represent a cirAE spectrum with a common underlying immunologic mechanism. Thus, understanding the immunopathogenesis of cirAEs can aid in their treatment and prevention.
免疫检查点抑制剂（ICI）治疗引起的皮肤免疫相关不良事件（cirAEs）与自发性炎症性皮肤病具有共同的临床特征。然而，cirAEs的确切免疫发病机制仍不清楚。
研究介导最常见的cirAEs，即苔藓样疹（LE）和湿疹样疹（EE）的炎症。
在一项前瞻性队列研究中，纳入接受ICI治疗且出现任何临床可见cirAEs的癌症患者。将cirAEs中的辅助性T细胞1（Th1）和Th2细胞反应与自发性苔藓样皮炎和湿疹样皮炎进行比较。
在收集的88份cirAE活检样本中，LE（35.22%）和EE（31.81%）占大多数病例。与苔藓样皮炎不同，我们发现ICI诱导的LE中CD4/CD8 T细胞和Th2/Th1比值升高，与EE相似。重要的是，我们在病理学上发现了几种同时表现为LE和EE的cirAEs。
仅评估了最常见类型的cirAEs，未分析Th17细胞。
我们的研究结果表明，LE和EE可能代表具有共同潜在免疫机制的cirAE谱。因此，了解cirAEs的免疫发病机制有助于其治疗和预防。
