Guglielmo Alba, Borghi Alessandro, Schettini Natale, Perillo Marcello, Corazza Monica, Piraccini Bianca Maria, Pileri Alessandro
Section of Dermatology, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Expert Rev Clin Immunol. 2025 Jun;21(6):723-729. doi: 10.1080/1744666X.2025.2507332. Epub 2025 May 17.
Dupilumab is a monoclonal antibody that inhibits the IL-4 receptor alpha, preventing the binding of IL-4 and IL-13 and the subsequent signal transduction. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common form of cutaneous T-cell lymphoma (CTCL). Several cases of MF have been reported following the initiation of dupilumab in patients previously diagnosed with atopic dermatitis.
This article is a narrative review of the current state of knowledge regarding the correlation between dupilumab and the development of CTCL. Clinical studies on this topic are reviewed, with a particular focus on the pathogenetic theories proposed to date. Finally, we present a new theory, previously undescribed, regarding the potential role of the cytokine microenvironment in triggering CTCL in patients treated with dupilumab.
Dupilumab could unmask CTCLs by inhibiting IL-4. In fact, a recent study observed that IL-4 plays a key role in maintaining the 'equilibrium phase' between tumor and microenvironment cells. Disruption of this balance could promote the escape of tumor cells and lead to the unmasking of CTCLs.
度普利尤单抗是一种单克隆抗体,可抑制白细胞介素-4受体α,阻止白细胞介素-4和白细胞介素-13的结合以及随后的信号转导。蕈样肉芽肿(MF)和塞扎里综合征(SS)是皮肤T细胞淋巴瘤(CTCL)最常见的形式。已有数例在先前诊断为特应性皮炎的患者中使用度普利尤单抗后发生MF的病例报告。
本文是一篇关于度普利尤单抗与CTCL发生之间相关性的现有知识的叙述性综述。对该主题的临床研究进行了综述,特别关注迄今为止提出的发病机制理论。最后,我们提出了一种新的、此前未描述过的理论,即细胞因子微环境在接受度普利尤单抗治疗的患者中触发CTCL的潜在作用。
度普利尤单抗可能通过抑制白细胞介素-4而使CTCL显现出来。事实上,最近一项研究观察到白细胞介素-4在维持肿瘤细胞与微环境细胞之间的“平衡期”中起关键作用。这种平衡的破坏可能促进肿瘤细胞的逃逸并导致CTCL的显现。