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...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1515250/full |
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| 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 |
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| 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. |
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| 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 |
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