Spatially Resolved Tumor Microenvironment Predicts Treatment Outcomes in Relapsed/Refractory Hodgkin Lymphoma.

Autor:	Aoki T; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.; Princess Margaret Cancer Centre-University Health Network, Toronto, Ontario, Canada., Jiang A; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Xu A; Cedars-Sinai Medical Center, Los Angeles, CA., Yin Y; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada., Gamboa A; Cedars-Sinai Medical Center, Los Angeles, CA., Milne K; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Takata K; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada.; Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Miyata-Takata T; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada., Chung S; Leukemia/Bone Marrow Transplant Program of BC, BC Cancer, Vancouver, British Columbia, Canada., Rai S; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada., Wu S; Department of Molecular Oncology, BC Cancer, Vancouver, BC, Canada., Warren M; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Strong C; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Goodyear T; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Morris K; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Chong LC; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada., Hav M; Cedars-Sinai Medical Center, Los Angeles, CA., Colombo AR; Cedars-Sinai Medical Center, Los Angeles, CA., Telenius A; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada., Boyle M; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada., Ben-Neriah S; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada., Power M; Leukemia/Bone Marrow Transplant Program of BC, BC Cancer, Vancouver, British Columbia, Canada., Gerrie AS; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada., Weng AP; Terry Fox Laboratory, BC Cancer, Vancouver, British Columbia, Canada., Karsan A; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.; Michael Smith Genome Sciences Centre, BC Cancer Research Institute, Vancouver, BC, Canada., Roth A; Department of Molecular Oncology, BC Cancer, Vancouver, BC, Canada., Farinha P; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Scott DW; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada., Savage KJ; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada., Nelson BH; Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada., Merchant A; Cedars-Sinai Medical Center, Los Angeles, CA., Steidl C; Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Mar 20; Vol. 42 (9), pp. 1077-1087. Date of Electronic Publication: 2023 Dec 19.
DOI:	10.1200/JCO.23.01115
Abstrakt:	Purpose: About a third of patients with relapsed or refractory classic Hodgkin lymphoma (r/r CHL) succumb to their disease after high-dose chemotherapy followed by autologous stem-cell transplantation (HDC/ASCT). Here, we aimed to describe spatially resolved tumor microenvironment (TME) ecosystems to establish novel biomarkers associated with treatment failure in r/r CHL. Patients and Methods: We performed imaging mass cytometry (IMC) on 71 paired primary diagnostic and relapse biopsies using a marker panel specific to CHL biology. For each cell type in the TME, we calculated a spatial score measuring the distance of nearest neighbor cells to the malignant Hodgkin Reed Sternberg cells within the close interaction range. Spatial scores were used as features in prognostic model development for post-ASCT outcomes. Results: Highly multiplexed IMC data revealed shared TME patterns in paired diagnostic and early r/r CHL samples, whereas TME patterns were more divergent in pairs of diagnostic and late relapse samples. Integrated analysis of IMC and single-cell RNA sequencing data identified unique architecture defined by CXCR5 + Hodgkin and Reed Sternberg (HRS) cells and their strong spatial relationship with CXCL13+ macrophages in the TME. We developed a prognostic assay (RHL4S) using four spatially resolved parameters, CXCR5+ HRS cells, PD1+CD4 + T cells, CD68 + tumor-associated macrophages, and CXCR5+ B cells, which effectively separated patients into high-risk versus low-risk groups with significantly different post-ASCT outcomes. The RHL4S assay was validated in an independent r/r CHL cohort using a multicolor immunofluorescence assay. Conclusion: We identified the interaction of CXCR5+ HRS cells with ligand-expressing CXCL13+ macrophages as a prominent crosstalk axis in relapsed CHL. Harnessing this TME biology, we developed a novel prognostic model applicable to r/r CHL biopsies, RHL4S, opening new avenues for spatial biomarker development.
Databáze:	MEDLINE
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