Aoki Tomohiro, Wierzbicki Kyle, Sun Suhong, Steidl Christian, Giulino-Roth Lisa
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Department of Medicine, University of Toronto, Toronto, ON, United States.
Front Oncol. 2025 May 1;15:1515250. doi: 10.3389/fonc.2025.1515250. eCollection 2025.
Classic Hodgkin lymphoma (cHL) exhibits a bimodal age distribution with incidence peaks in adolescents and young adults (AYAs) aged 15-39 years and in older adults over 50 years. The unique biology of cHL, characterized by a tumor microenvironment (TME) composed predominantly of non-malignant immune and stromal cells, plays a pivotal role in supporting Hodgkin and Reed-Sternberg (HRS) cells, the malignant cells of cHL. Understanding the role of the TME in cHL and its age-related differences is crucial for deciphering differential disease etiologies and developing biomarker-driven targeted therapies. Recent technical advances in single-cell sequencing and multiplexed spatial imaging have revealed age-related differences in TME composition and function, including key cellular interactions, leading to the development of age-specific prognostic indicators. In addition, advances in our ability to isolate nucleic acids from HRS cells have accelerated our understanding of the molecular alterations in cHL, many of which drive interactions within the TME. Molecular differences in cHL between pediatric/AYA and older adult patients have also emerged. This review summarizes the unique biology of cHL and its TME in children, adolescents, and young adults, highlighting recent breakthroughs in our understanding of cHL biology, differences across the age spectrum, and advances in biomarker development.
经典型霍奇金淋巴瘤（cHL）呈现双峰年龄分布，发病高峰出现在15至39岁的青少年和青年（AYA）以及50岁以上的老年人中。cHL独特的生物学特性，其特征为主要由非恶性免疫和基质细胞组成的肿瘤微环境（TME），在支持霍奇金和里德-斯腾伯格（HRS）细胞（cHL的恶性细胞）方面发挥着关键作用。了解TME在cHL中的作用及其与年龄相关的差异对于解读不同的疾病病因和开发基于生物标志物的靶向治疗至关重要。单细胞测序和多重空间成像技术的最新进展揭示了TME组成和功能方面与年龄相关的差异，包括关键的细胞间相互作用，从而促成了特定年龄的预后指标的发展。此外，我们从HRS细胞中分离核酸能力的进步加速了我们对cHL分子改变的理解，其中许多改变驱动了TME内的相互作用。儿科/AYA患者与老年患者之间cHL的分子差异也已显现。本综述总结了cHL及其在儿童、青少年和青年中的TME的独特生物学特性，强调了我们对cHL生物学理解的最新突破、不同年龄阶段的差异以及生物标志物开发的进展。
