Related Experiment Video
Updated: Feb 17, 2026
08:53
Flow-sorting and Exome Sequencing of the Reed-Sternberg Cells of Classical Hodgkin Lymphoma
Published on: June 10, 2017
10.5K
High-Resolution Spatial Transcriptomic Characterization of Syncytial Variant of Nodular Sclerosis Classical Hodgkin
Xiaoyue Xiao1, Jiyan Dong1, Xujie Sun1
1Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Laboratory Investigation; a Journal of Technical Methods and Pathology
|February 15, 2026
Summary
The syncytial variant of nodular sclerosis classical Hodgkin Lymphoma (SV-NSCHL) has a complex tumor microenvironment (TME) with suppressed immunity. This study identifies PEG10 as a key gene linked to poor outcomes and immune evasion in SV-NSCHL.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- The syncytial variant of nodular sclerosis classical Hodgkin Lymphoma (SV-NSCHL) is linked to worse patient outcomes.
- The tumor microenvironment (TME) complexity in SV-NSCHL remains poorly understood, hindering therapeutic development.
Purpose of the Study:
- To comprehensively map and compare the TME in SV-NSCHL versus common nodular sclerosis classical Hodgkin Lymphoma (cNSCHL).
- To identify key molecular drivers and immune evasion mechanisms in SV-NSCHL.
Main Methods:
- Spatial transcriptomics (Xenium In Situ) on 10 lymphoma specimens (4 cNSCHL, 4 SV-NSCHL, 2 reactive lymph nodes).
- Profiling of 317,762 cells to analyze tumor cells and immune microenvironment.
- Immunohistochemistry (IHC) validation of PEG10 expression in an independent cohort (n=121).
Main Results:
- Paternally expressed gene (PEG10) was significantly upregulated in SV-NSCHL Hodgkin Reed-Sternberg (HRS) cells, correlating with proliferation and inferior progression-free survival (PFS).
- SV-NSCHL exhibited an immunosuppressive TME: depleted CD8+ T cells, expanded regulatory T cells (Tregs), altered B cells, and M2-like macrophages.
- Upregulated inhibitory ligand-receptor interactions between HRS cells and Tregs were observed in SV-NSCHL.
Conclusions:
- This study presents the first spatial atlas of SV-NSCHL, implicating PEG10 in HRS cell proliferation and poor prognosis.
- Identified actionable immune evasion signatures in SV-NSCHL provide a roadmap for novel targeted therapies.
