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靶向 PD-1 和 PD-L1 的免疫检查点抑制剂相关的自身免疫性大疱性皮肤病。

Autoimmune Bullous Skin Disorders with Immune Checkpoint Inhibitors Targeting PD-1 and PD-L1.

机构信息

Department of Oncology, Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland.

Department of Dermatology and Dermato-oncology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.

出版信息

Cancer Immunol Res. 2016 May;4(5):383-9. doi: 10.1158/2326-6066.CIR-15-0123. Epub 2016 Feb 29.

Abstract

Monoclonal antibodies (mAb) targeting immune checkpoint pathways such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) may confer durable disease control in several malignancies. In some patients, immune checkpoint mAbs cause cutaneous immune-related adverse events. Although the most commonly reported cutaneous toxicities are mild, a subset may persist despite therapy and can lead to severe or life-threatening toxicity. Autoimmune blistering disorders are not commonly associated with immune checkpoint mAb therapy. We report a case series of patients who developed bullous pemphigoid (BP), an autoimmune process classically attributed to pathologic autoantibody formation and complement deposition. Three patients were identified. Two patients developed BP while receiving the anti-PD-1 mAb nivolumab, and one while receiving the anti-PD-L1 mAb durvalumab. The clinicopathologic features of each patient and rash, and corresponding radiologic findings at the development of the rash and after its treatment, are described. Patients receiving an anti-PD-1/PD-L1 mAb may develop immune-related BP. This may be related to both T-cell- and B-cell-mediated responses. Referral to a dermatologist for accurate diagnosis and management is recommended. Cancer Immunol Res; 4(5); 383-9. ©2016 AACR.

摘要

单克隆抗体(mAb)针对免疫检查点途径,如细胞毒性 T 淋巴细胞相关蛋白 4(CTLA-4)和程序性死亡 1(PD-1),可能在几种恶性肿瘤中提供持久的疾病控制。在一些患者中,免疫检查点 mAb 引起皮肤免疫相关不良事件。虽然最常报告的皮肤毒性是轻度的,但一些患者尽管接受了治疗仍可能持续存在,并可能导致严重或危及生命的毒性。自身免疫性水疱性疾病通常与免疫检查点 mAb 治疗无关。我们报告了一系列发生大疱性类天疱疮(BP)的患者,BP 是一种自身免疫过程,通常归因于病理性自身抗体形成和补体沉积。确定了 3 名患者。2 名患者在接受抗 PD-1 mAb 纳武单抗治疗时发生 BP,1 名患者在接受抗 PD-L1 mAb 度伐单抗治疗时发生 BP。描述了每位患者的临床病理特征以及皮疹,以及皮疹发生时和治疗后的皮疹和相应的放射学发现。接受抗 PD-1/PD-L1 mAb 治疗的患者可能会发生免疫相关的 BP。这可能与 T 细胞和 B 细胞介导的反应有关。建议向皮肤科医生转诊以进行准确诊断和管理。癌症免疫治疗研究;4(5);383-9。©2016AACR。

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