Kurlapski Michał, Braczko Alicja, Dubiela Paweł, Walczak Iga, Kutryb-Zając Barbara, Zaucha Jan Maciej
Department of Hematology and Transplantology, University Clinical Centre, Medical University of Gdansk, 80-211 Gdańsk, Poland.
Department of Biochemistry, Medical University of Gdansk, 80-211 Gdańsk, Poland.
Int J Mol Sci. 2025 Aug 4;26(15):7508. doi: 10.3390/ijms26157508.
Classical Hodgkin lymphoma (cHL) is a biologically and clinically unique malignancy characterized by rare Hodgkin and Reed-Sternberg (HRS) cells surrounded by a dense and diverse inflammatory infiltrate. These malignant cells actively reshape the tumor microenvironment (TME) through metabolic reprogramming and immune evasion strategies. This review synthesizes current knowledge on how metabolic alterations contribute to tumor survival, immune dysfunction, and therapeutic resistance in cHL. We discuss novel therapeutic approaches aimed at disrupting these processes and examine the potential of combining metabolic interventions with immune-based strategies-such as immune checkpoint inhibitors (CPIs), epigenetic modulators, bispecific antibodies, and CAR-T/CAR-NK cell therapies-which may help overcome resistance and enhance anti-tumor responses. Several agents are currently under investigation for their ability to modulate immune cell metabolism and restore effective immune surveillance. Altogether, targeting metabolic vulnerabilities within both tumor and immune compartments offers a promising, multifaceted strategy to improve clinical outcomes in patients with relapsed or refractory cHL.
经典型霍奇金淋巴瘤（cHL）是一种在生物学和临床上具有独特性的恶性肿瘤，其特征是罕见的霍奇金和里德-斯腾伯格（HRS）细胞被密集且多样的炎性浸润所包围。这些恶性细胞通过代谢重编程和免疫逃逸策略积极重塑肿瘤微环境（TME）。本综述综合了关于代谢改变如何促进cHL肿瘤存活、免疫功能障碍和治疗抵抗的当前知识。我们讨论了旨在破坏这些过程的新型治疗方法，并研究了将代谢干预与基于免疫的策略（如免疫检查点抑制剂（CPI）、表观遗传调节剂、双特异性抗体以及CAR-T/CAR-NK细胞疗法）相结合的潜力，这些策略可能有助于克服耐药性并增强抗肿瘤反应。目前正在研究几种药物调节免疫细胞代谢和恢复有效免疫监视的能力。总之，针对肿瘤和免疫区室中的代谢弱点提供了一种有前景的多方面策略，以改善复发或难治性cHL患者的临床结局。
