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Multidimensional Characterization of Tumor-Immune Architecture Reveals Clinically Relevant Classic Hodgkin Lymphoma Subtypes.

Cancer discovery 2026

Aoki T, Duns G, Rai S, Jiang A, Lytle A, Yin Y, Kishida M, Yu Li M, Lee C, Smorra D, Hilton LK, Healy S, Alig SK, Shahrokh Esfahani M, Sarkozy C, Hung SS, Milne K, Telenius A, O Brien L, Wong JC, Cassidy C, Fujisawa M, Strong C, Goodyear T, Di Vito C, Luksik C, Edin G, Gonzalez L, Rangel Patiño J, Hong M, Wu S, Lee E, Sakhdari A, Takata K, Miyata-Takata T, Boyle M, Ben-Neriah S, Weng AP, Xu A, Merchant A, Roth A, Crump M, Kuruvilla J, Prica A, Kridel R, Huntsman DG, Nelson BH, Farinha P, Morin RD, Alizadeh AA, Savage KJ, Scott DW, Steidl C

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The tissue architecture of classic Hodgkin Lymphoma (CHL) is unique among cancers and characterized by rare malignant Hodgkin and Reed-Sternberg cells that co-evolve with a complex ecosystem of immune

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BibTeX ↓ RIS ↓
APA Aoki T, Duns G, et al. (2026). Multidimensional Characterization of Tumor-Immune Architecture Reveals Clinically Relevant Classic Hodgkin Lymphoma Subtypes.. Cancer discovery. https://doi.org/10.1158/2159-8290.CD-25-0859
MLA Aoki T, et al.. "Multidimensional Characterization of Tumor-Immune Architecture Reveals Clinically Relevant Classic Hodgkin Lymphoma Subtypes.." Cancer discovery, 2026.
PMID 41615883
DOI 10.1158/2159-8290.CD-25-0859

Abstract

The tissue architecture of classic Hodgkin Lymphoma (CHL) is unique among cancers and characterized by rare malignant Hodgkin and Reed-Sternberg cells that co-evolve with a complex ecosystem of immune cells in the tumor microenvironment (TME). The lack of a comprehensive systems-level interrogation has hindered the description of disease heterogeneity and clinically relevant molecular subtypes. Here, we employed an integrative, multimodal approach to characterize CHL tumors using malignant cell sequencing, spatial transcriptomics and imaging mass cytometry. We identified four molecular subtypes (CST, CN913, STB, and CN2P), each characterized by distinct clinical features, mutational patterns, malignant cell gene expression profiles, and spatial architecture involving immune cell populations. Functional modeling of CSF2RB mutations, a characteristic feature of the CST subtype, revealed dysregulated oncogenic signaling and unique TME crosstalk. These findings highlight the significance of multi-dimensional profiling in elucidating patterns of molecular alterations that drive immune ecosystems and underlie therapeutically exploitable vulnerabilities.

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