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Updated: Jun 22, 2025
Flow-sorting and Exome Sequencing of the Reed-Sternberg Cells of Classical Hodgkin Lymphoma
Published on: June 10, 2017
Multiplexed Spatial Profiling of Hodgkin Reed-Sternberg Cell Neighborhoods in Classic Hodgkin Lymphoma
Maryam Pourmaleki1,2,3, Caitlin J Jones4, Sabrina D Mellinghoff1
1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Purpose:
Classic Hodgkin lymphoma (cHL) is a B-cell lymphoma that occurs primarily in young adults and, less frequently, in elderly individuals. A hallmark of cHL is the exceptional scarcity (1%-5%) of the malignant Hodgkin Reed-Sternberg (HRS) cells within a network of nonmalignant immune cells. Molecular determinants governing the relationship between HRS cells and their proximal microenvironment remain largely unknown.
Experimental Design:
We performed spatially resolved multiplexed protein imaging and transcriptomic sequencing to characterize HRS cell states, cellular neighborhoods, and gene expression signatures of 23.6 million cells from 36 newly diagnosed Epstein-Barr virus (EBV)-positive and EBV-negative cHL tumors.
Results:
We show that MHC-I expression on HRS cells is associated with immune-inflamed neighborhoods containing CD8+ T cells, MHC-II+ macrophages, and immune checkpoint expression (i.e., PD1 and VISTA). We identified spatial clustering of HRS cells, consistent with the syncytial variant of cHL, and its association with T-cell-excluded neighborhoods in a subset of EBV-negative tumors. Finally, a subset of both EBV-positive and EBV-negative tumors contained regulatory T-cell-high neighborhoods harboring HRS cells with augmented proliferative capacity.
Conclusions:
Our study links HRS cell properties with distinct immunophenotypes and potential immune escape mechanisms in cHL.
