Schaberg Kurt B, Novoa Roberto A, Wakelee Heather A, Kim Jinah, Cheung Christine, Srinivas Sandhya, Kwong Bernice Y
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
J Cutan Pathol. 2016 Apr;43(4):339-46. doi: 10.1111/cup.12666. Epub 2016 Feb 10.
Recent advances in the immunotherapeutic treatment of cancer have led to the development of multiple new directed therapies including monoclonal antibodies that block the immune checkpoint T-cell receptor programmed death 1 (PD-1) and the PD-1 ligand, programmed death ligand 1 (PD-L1). Various immune-related toxicities have been associated with these drugs including, most commonly, skin rashes.
Five cases of lichenoid dermatitis, including one case of lichenoid mucositis and one case of lichen sclerosus, associated with anti-PD-L1 and anti-PD1 therapy were compared with three biopsies of non-drug-related lichen planus (LP) and three lichen planus-like keratoses (LPLK) used as controls.
Histopathologic and immunophenotypic analysis of these lichenoid lesions demonstrated significantly greater histiocytic infiltrates than observed in control lichenoid reactions (p = 0.0134). We also observed increased spongiosis and epidermal necrosis. No significant differences were seen in expression of CD3, CD4:CD8, CD20, PD-1, CD25, Foxp3, CXCL13 and PD-L1 expression.
These findings expand the literature of immune-related toxicities of PD-L1 and PD-1 blockade to include lichenoid dermatitis and lichenoid mucositis. Of note, these cutaneous side effects were amenable to topical treatment, without the need for medication dose reduction or discontinuation.
癌症免疫治疗的最新进展促使多种新型靶向治疗方法得以开发,包括阻断免疫检查点T细胞受体程序性死亡蛋白1(PD-1)及其配体程序性死亡配体1(PD-L1)的单克隆抗体。这些药物与多种免疫相关毒性有关,其中最常见的是皮疹。
将5例与抗PD-L1和抗PD-1治疗相关的苔藓样皮炎病例(包括1例苔藓样黏膜病和1例硬化性苔藓)与3例非药物相关性扁平苔藓(LP)活检标本及3例扁平苔藓样角化病(LPLK)作为对照进行比较。
这些苔藓样病变的组织病理学和免疫表型分析显示,与对照性苔藓样反应相比,组织细胞浸润明显更多(p = 0.0134)。我们还观察到海绵形成增加和表皮坏死。在CD3、CD4:CD8、CD20、PD-1、CD25、Foxp3、CXCL13和PD-L1表达方面未观察到显著差异。
这些发现扩展了PD-L1和PD-1阻断免疫相关毒性的文献,使其包括苔藓样皮炎和苔藓样黏膜病。值得注意的是,这些皮肤副作用适合局部治疗,无需减少药物剂量或停药。