Synapse - Multiplexed spatial profiling of Hodgkin Reed–Sternberg cell neighborhoods in classic Hodgkin lymphoma

Multiplexed spatial profiling of Hodgkin Reed–Sternberg cell neighborhoods in classic Hodgkin lymphoma Journal Article

Authors:	Pourmaleki, M.; Jones, C. J.; Mellinghoff, S. D.; Greenstein, B. D.; Kumar, P.; Foronda, M.; Navarrete, D. A.; Campos, C.; Roshal, M.; Schultz, N.; Shah, S. P.; Schietinger, A.; Socci, N. D.; Hollmann, T. J.; Dogan, A.; Mellinghoff, I. K.
Article Title:	Multiplexed spatial profiling of Hodgkin Reed–Sternberg cell neighborhoods in classic Hodgkin lymphoma
Abstract:	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. ©2024 The Authors; Published by the American Association for Cancer Research.
Keywords:	immunohistochemistry; signal transduction; adult; human tissue; protein expression; aged; middle aged; human cell; cd8+ t lymphocyte; t lymphocyte; cd8-positive t-lymphocytes; quality control; phenotype; gene expression profiling; cytotoxicity; immunofluorescence; pathology; retrospective study; hodgkin disease; virology; in situ hybridization; b cell lymphoma; regulatory t lymphocyte; antigen presentation; immunology; algorithm; immunophenotyping; tissue microarray; molecular biology; macrophage; isolation and purification; transcriptome; immunocompetent cell; epstein barr virus; herpesvirus 4, human; histogram; classical hodgkin lymphoma; reed sternberg cell; reed-sternberg cells; epstein-barr virus infections; transcriptome sequencing; tumor microenvironment; complication; antibody conjugate; latent membrane protein 1; autofluorescence; epstein barr virus infection; humans; human; male; female; article; antigenic escape; multiplexed spatial profiling
Journal Title:	Clinical Cancer Research
Volume:	30
Issue:	17
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2024-09-01
Start Page:	3881
End Page:	3893
Language:	English
DOI:	10.1158/1078-0432.Ccr-24-0942
PUBMED:	38949890
PROVIDER:	scopus
PMCID:	PMC11369618
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85203205328&doi=10.1158%2f1078-0432.CCR-24-0942&partnerID=40&md5=70349786d9112770da442eb88c6480cd
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding authors are Ahmet Dogan and Ingo Mellinghoff -- Source: Scopus