Dupilumab-associated lymphoproliferative disorders: a comprehensive review on clinicohistopathologic features and underlying mechanisms

IF 6.6 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology Pub Date : 2025-05-10 DOI:10.1016/j.coi.2025.102563

Mingjia Li , Wei Zhao , Pan Lai , Yu Xiao , Yang Wang

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Abstract

Dupilumab, a monoclonal antibody targeting interleukin 4 receptor, has shown significant efficacy in treating atopic dermatitis (AD). However, emerging case reports indicate that it may unmask or cause cutaneous T cell lymphoma (CTCL). This review analyzes 29 studies involving 124 patients who developed lymphoproliferative disorders after dupilumab, including 13 cases of lymphoproliferative reactions not meeting lymphoma criteria.

The median time from dupilumab initiation to biopsy-confirmed lymphoproliferative disorders was 5 months, with 39.05% of cases in advanced stages. Histopathological examination of dupilumab-induced CTCL reveals epidermotropism with spongiosis and increased superficial lymphoid infiltration. Notably, early lymphoproliferative reaction shows subtle lymphoma features, characterized by perivascular infiltration with sprinkled intraepidermal lymphocytes, CD30 expression, and absence of clonal TCR rearrangement and T-cell markers loss. Adult-onset AD patients, particularly those with atypical skin lesions, short-term exacerbation, or no atopy history, should be closely monitored during dupilumab treatment, and skin biopsy is essential if no clinical improvement occurs. Discontinuation is recommended when lymphoid infiltration increases, even without typical lymphoma features.

The mechanisms underlying dupilumab-associated lymphoma remain speculative. Current hypotheses include upregulation of IL13RA2 signaling pathway, prolonged persistence of immune cell populations, and varying responses of different tumor cell subclusters. Additionally, the effects of dupilumab on various cell types are complex and multifaceted. Consequently, the distribution of type 2 inflammatory cytokine receptors and the patterns of cellular infiltration within the microenvironment may impact disease progression following dupilumab treatment. Further research is needed to clarify the mechanisms linking dupilumab to CTCL for better defining dupilumab's safety profile.

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杜匹单抗相关淋巴增生性疾病：临床组织病理学特征和潜在机制的综合综述

Dupilumab是一种靶向白介素4受体的单克隆抗体，在治疗特应性皮炎（AD）中显示出显著的疗效。然而，新出现的病例报告表明，它可能暴露或引起皮肤T细胞淋巴瘤（CTCL）。本综述分析了29项研究，涉及124例dupilumab治疗后出现淋巴增生性疾病的患者，包括13例不符合淋巴瘤标准的淋巴增生性反应。从dupilumab开始治疗到活检证实的淋巴增生性疾病的中位时间为5个月，其中39.05%的病例处于晚期。dupilumab诱导的CTCL的组织病理学检查显示嗜表皮性伴海绵状病和浅表淋巴细胞浸润增加。值得注意的是，早期淋巴增生性反应表现出轻微的淋巴瘤特征，其特征是血管周围浸润，表皮内淋巴细胞散布，CD30表达，无克隆性TCR重排和t细胞标记物丢失。成人发病的AD患者，特别是那些有非典型皮肤病变、短期加重或无特应性病史的患者，在dupilumab治疗期间应密切监测，如果没有临床改善，则必须进行皮肤活检。当淋巴浸润增加时，即使没有典型的淋巴瘤特征，也建议停药。杜匹单抗相关淋巴瘤的机制仍然是推测性的。目前的假说包括IL13RA2信号通路的上调、免疫细胞群的持续时间延长以及不同肿瘤细胞亚群的不同反应。此外，dupilumab对各种细胞类型的影响是复杂和多方面的。因此，微环境中2型炎症细胞因子受体的分布和细胞浸润模式可能影响杜匹单抗治疗后的疾病进展。为了更好地确定dupilumab的安全性，需要进一步的研究来阐明dupilumab与CTCL之间的联系机制。

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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来源期刊

Current Opinion in Immunology 医学-免疫学

CiteScore

13.30

自引率

1.40%

发文量

审稿时长

67 days

期刊介绍： Current Opinion in Immunology aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed. In Current Opinion in Immunology we help the reader by providing in a systematic manner: 1. The views of experts on current advances in their field in a clear and readable form. 2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications. Current Opinion in Immunology will serve as an invaluable source of information for researchers, lecturers, teachers, professionals, policy makers and students. Current Opinion in Immunology builds on Elsevier''s reputation for excellence in scientific publishing and long-standing commitment to communicating reproducible biomedical research targeted at improving human health. It is a companion to the new Gold Open Access journal Current Research in Immunology and is part of the Current Opinion and Research(CO+RE) suite of journals. All CO+RE journals leverage the Current Opinion legacy-of editorial excellence, high-impact, and global reach-to ensure they are a widely read resource that is integral to scientists'' workflow.