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MINI REVIEW article
Front. Oncol.
Sec. Pediatric Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1515250
This article is part of the Research Topic The Tumor Immune Microenvironment in Pediatric Cancers View all 5 articles
Tumor-microenvironment and molecular biology of classic Hodgkin lymphoma in children, adolescents, and young adults
Provisionally accepted- 1 Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada
- 2 Weill Cornell Medicine, Cornell University, New York, New York, United States
- 3 University of British Columbia, Vancouver, British Columbia, Canada
- 4 Weill Cornell Medical Center, NewYork-Presbyterian, New York City, United States
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 agespecific 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.
Keywords: Hodgkin lymphoma (HL), pediatric, TME (tumor microenvironment), Genetics, Reed Sternberg cells
Received: 22 Oct 2024; Accepted: 31 Mar 2025.
Copyright: © 2025 Aoki, Wierzbicki, Sun, Steidl and Roth. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lisa Roth, Weill Cornell Medical Center, NewYork-Presbyterian, New York City, United States
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