Andreescu Mihaela, Tudorache Sorin Ioan, Moldovan Cosmin Alec, Andreescu Bogdan
Department of Clinical Sciences, Hematology, Faculty of Medicine, Titu Maiorescu University of Bucharest, 040051 Bucharest, Romania.
Department of Hematology, Colentina Clinical Hospital, 020125 Bucharest, Romania.
Curr Issues Mol Biol. 2025 Jul 24;47(8):586. doi: 10.3390/cimb47080586.
Mycosis fungoides (MF), the most prevalent cutaneous T cell lymphoma, features clonal CD4⁺ T cell proliferation within a Th2-dominant microenvironment. Interleukin-4 (IL-4) promotes disease progression while Brentuximab Vedotin (BV), an anti-CD30 antibody-drug conjugate, shows efficacy but faces resistance challenges.
We conducted a narrative literature review (2010-2024) synthesizing evidence on IL-4 signaling and BV's efficacy in MF to develop a theoretical framework for combination therapy.
IL-4 may modulate CD30 expression and compromise BV's effectiveness through immunosuppressive microenvironment remodeling. Theoretical mechanisms suggest that IL-4 pathway inhibition could reprogram the microenvironment toward Th1 dominance and restore BV sensitivity. However, no direct experimental evidence validates this combination, and safety concerns including potential disease acceleration require careful evaluation.
The proposed IL-4/BV combination represents a biologically compelling but unproven hypothesis requiring systematic preclinical validation and biomarker-driven clinical trials. This framework could guide future research toward transforming treatment approaches for CD30-positive MF by targeting both malignant cells and their immunologically permissive microenvironment.
蕈样肉芽肿（MF）是最常见的皮肤T细胞淋巴瘤，其特征是在以Th2为主导的微环境中克隆性CD4⁺ T细胞增殖。白细胞介素-4（IL-4）促进疾病进展，而抗CD30抗体药物偶联物本妥昔单抗（BV）显示出疗效，但面临耐药性挑战。
我们进行了一项叙述性文献综述（2010 - 2024年），综合了关于IL-4信号传导和BV在MF中的疗效的证据，以建立联合治疗的理论框架。
IL-4可能通过重塑免疫抑制微环境来调节CD30表达并损害BV的有效性。理论机制表明，抑制IL-4途径可使微环境重新编程为Th1主导并恢复BV敏感性。然而，没有直接的实验证据证实这种联合，包括潜在疾病加速在内的安全性问题需要仔细评估。
提议的IL-4/BV联合方案代表了一个生物学上有说服力但未经证实的假设，需要系统的临床前验证和生物标志物驱动的临床试验。该框架可为未来研究提供指导，通过靶向恶性细胞及其免疫许可微环境来改变CD30阳性MF的治疗方法。
