Tumor-microenvironment and molecular biology of classic Hodgkin lymphoma in children, adolescents, and young adults

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Tomohiro Aoki, Kyle Wierzbicki, Suhong Sun, Christian Steidl, Lisa Giulino-Roth
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1515250/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850260185320259584
author Tomohiro Aoki
Tomohiro Aoki
Kyle Wierzbicki
Suhong Sun
Christian Steidl
Christian Steidl
Lisa Giulino-Roth
author_facet Tomohiro Aoki
Tomohiro Aoki
Kyle Wierzbicki
Suhong Sun
Christian Steidl
Christian Steidl
Lisa Giulino-Roth
author_sort Tomohiro Aoki
collection DOAJ
description 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.
format Article
id doaj-art-9d8c0b5025d74bbe835f913bf71e0964
institution OA Journals
issn 2234-943X
language English
publishDate 2025-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj-art-9d8c0b5025d74bbe835f913bf71e09642025-08-20T01:55:41ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-05-011510.3389/fonc.2025.15152501515250Tumor-microenvironment and molecular biology of classic Hodgkin lymphoma in children, adolescents, and young adultsTomohiro Aoki0Tomohiro Aoki1Kyle Wierzbicki2Suhong Sun3Christian Steidl4Christian Steidl5Lisa Giulino-Roth6Princess Margaret Cancer Centre, University Health Network, Toronto, ON, CanadaDepartment of Medicine, University of Toronto, Toronto, ON, United StatesDepartment of Pediatrics, Weill Cornell Medicine, New York, NY, United StatesDepartment of Pediatrics, Weill Cornell Medicine, New York, NY, United StatesCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Pediatrics, Weill Cornell Medicine, New York, NY, United StatesClassic 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.https://www.frontiersin.org/articles/10.3389/fonc.2025.1515250/fullHodgkin lymphoma (HL)pediatricTME (tumor microenvironment)geneticsHodgkin and Reed-Sternberg cells
spellingShingle Tomohiro Aoki
Tomohiro Aoki
Kyle Wierzbicki
Suhong Sun
Christian Steidl
Christian Steidl
Lisa Giulino-Roth
Tumor-microenvironment and molecular biology of classic Hodgkin lymphoma in children, adolescents, and young adults
Frontiers in Oncology
Hodgkin lymphoma (HL)
pediatric
TME (tumor microenvironment)
genetics
Hodgkin and Reed-Sternberg cells
title Tumor-microenvironment and molecular biology of classic Hodgkin lymphoma in children, adolescents, and young adults
title_full Tumor-microenvironment and molecular biology of classic Hodgkin lymphoma in children, adolescents, and young adults
title_fullStr Tumor-microenvironment and molecular biology of classic Hodgkin lymphoma in children, adolescents, and young adults
title_full_unstemmed Tumor-microenvironment and molecular biology of classic Hodgkin lymphoma in children, adolescents, and young adults
title_short Tumor-microenvironment and molecular biology of classic Hodgkin lymphoma in children, adolescents, and young adults
title_sort tumor microenvironment and molecular biology of classic hodgkin lymphoma in children adolescents and young adults
topic Hodgkin lymphoma (HL)
pediatric
TME (tumor microenvironment)
genetics
Hodgkin and Reed-Sternberg cells
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1515250/full
work_keys_str_mv AT tomohiroaoki tumormicroenvironmentandmolecularbiologyofclassichodgkinlymphomainchildrenadolescentsandyoungadults
AT tomohiroaoki tumormicroenvironmentandmolecularbiologyofclassichodgkinlymphomainchildrenadolescentsandyoungadults
AT kylewierzbicki tumormicroenvironmentandmolecularbiologyofclassichodgkinlymphomainchildrenadolescentsandyoungadults
AT suhongsun tumormicroenvironmentandmolecularbiologyofclassichodgkinlymphomainchildrenadolescentsandyoungadults
AT christiansteidl tumormicroenvironmentandmolecularbiologyofclassichodgkinlymphomainchildrenadolescentsandyoungadults
AT christiansteidl tumormicroenvironmentandmolecularbiologyofclassichodgkinlymphomainchildrenadolescentsandyoungadults
AT lisagiulinoroth tumormicroenvironmentandmolecularbiologyofclassichodgkinlymphomainchildrenadolescentsandyoungadults