Pacha Omar, Patel Anisha B, Curry Jonathan L, Haymaker Cara L, Ozirmak Lermi Nejla, Duose Dzifa Yawa, Chen Ken, Hajjar Joud, Naing Aung
Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
J Immunother Cancer. 2025 Aug 7;13(8):e011401. doi: 10.1136/jitc-2024-011401.
Although immune checkpoint inhibitors (ICIs) are efficacious, they often cause immune-related adverse events (irAEs), most commonly cutaneous irAEs (CirAEs). The mechanisms underlying CirAEs remain unclear.
Attempting to better understand their mechanisms and histology we conducted a prospective study of 15 patients with advanced cancers treated with ICIs who developed grade 2 or higher CirAEs. Clinical and histologic characterization of biopsy specimens of CirAEs was performed. Histologic analysis of patient biopsy specimens were subdivided by epidermal reaction patterns that included spongiotic, lichenoid, and interface dermatitis patterns. A targeted RNA expression assay was used to identify immune markers in CirAE lesions and adjacent unaffected skin samples.
Compared with adjacent unaffected skin, CirAE lesions had significantly upregulated () and increased M2 macrophages (adjusted p<0.05). Our findings suggest that CirAEs exhibit diverse histologic patterns that may mimic autoimmune skin diseases. The lack of distinct biomarker signatures may indicate complex and heterogeneous mechanisms underlying CirAEs; however, the upregulation of and elevated numbers of M2 macrophages in CirAE lesions suggest and M2 macrophages may be involved in the pathogenesis of these toxic effects. Further investigation to elucidate the molecular determinants of CirAEs and develop targeted therapeutic strategies is warranted.
尽管免疫检查点抑制剂（ICIs）有效，但它们常引发免疫相关不良事件（irAEs），最常见的是皮肤irAEs（CirAEs）。CirAEs的潜在机制仍不清楚。
为了更好地了解其机制和组织学，我们对15例接受ICIs治疗且发生2级或更高级别CirAEs的晚期癌症患者进行了一项前瞻性研究。对CirAEs活检标本进行了临床和组织学特征分析。患者活检标本的组织学分析根据表皮反应模式进行细分，包括海绵状、苔藓样和界面性皮炎模式。使用靶向RNA表达测定法来鉴定CirAE病变和相邻未受影响皮肤样本中的免疫标志物。
与相邻未受影响的皮肤相比，CirAE病变中 显著上调（）且M2巨噬细胞增加（校正p<0.05）。我们的研究结果表明，CirAEs表现出多种组织学模式，可能类似于自身免疫性皮肤病。缺乏独特的生物标志物特征可能表明CirAEs背后存在复杂和异质性的机制；然而，CirAE病变中 的上调和M2巨噬细胞数量的增加表明 和M2巨噬细胞可能参与了这些毒性作用的发病机制。有必要进一步研究以阐明CirAEs的分子决定因素并制定靶向治疗策略。
