---
title: "Spatial transcriptomics reveals a T-cell–excluded, suppressive tumor microenvironment in extramedu"
id: "pubmed-42379250"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42379250"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42379250/"
doi: "10.1182/bloodadvances.2026020500"
published_at: "2026-09-22T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Spatial transcriptomics reveals a T-cell–excluded, suppressive tumor microenvironment in extramedu
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42379250
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42379250/)
- **DOI:** [10.1182/bloodadvances.2026020500](https://doi.org/10.1182%2Fbloodadvances.2026020500)
- **Published At:** 2026-09-22T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Extramedullary disease (EMD) in multiple myeloma (MM) is linked to poor prognosis due to aggressive behavior and therapy resistance. Spatial transcriptomics was used to characterize tissue architecture in EMD tumor biopsies. - Tumor plasma cells (PCs) retained a characteristic **plasma cell** transcriptome but showed marked interpatient heterogeneity in expression profiles, similar to marrow-restricted MM. - The tumor microenvironment (TME) of EMD was dominated by macrophages with a suppressive **M2** phenotype and contained CD8+ T cells that frequently expressed exhaustion markers **LAG3** and **TIGIT**, consistent with immune suppression. - Three recurrent spatial TME niches were identified: **immune-excluded**, **immune-suppressed**, and **immune-permissive**. The **immune-excluded** niche comprised the majority of tumor regions and was characterized by spatial exclusion of immune cells from tumor regions. - An abundant population of tumor-associated **fibroblasts** produced a suppressive extracellular matrix (ECM) in the immune-suppressed niche, which may further impede T-cell infiltration and function. - Cell-cell interaction modeling indicated bidirectional signaling: PCs modulated the TME via **PGE2** and **VEGFB**, while receiving prosurvival inputs through receptors/signals including **CD38**, **CXCR4**, and **BCMA**. - TME components, notably fibroblasts and macrophages, are predicted to cooperatively promote the suppressive macrophage phenotype and fibrotic ECM, reinforcing local immunosuppression and supporting disease progression. - The spatial data support a model of niche substitution (adoption of local tissue microenvironments) rather than complete niche independence for EMD and identify microenvironmental niches and signaling networks that may be clinically actionable in this high-risk MM subset.
## Clinical Analysis & Structured Key Points
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more resources ](https://pubmed.ncbi.nlm.nih.gov/42379250/#linkout) Title & authors Abstract Conflict of interest statement Figures Similar articles References MeSH terms Related information LinkOut - more resources Blood Adv Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Blood+Adv%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Blood+Adv%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42379250/) . 2026 Sep 22;10(18):6221-6235. doi: 10.1182/bloodadvances.2026020500. # Spatial transcriptomics identifies a suppressive, T-cell-excluded tumor microenvironment in extramedullary myeloma [Nicholas E Bingham](https://pubmed.ncbi.nlm.nih.gov/?term=Bingham+NE&cauthor_id=42379250)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-1 "Clinical Haematology, Alfred Health, Melbourne, Australia.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-2 "Australian Centre for Blood Diseases, Monash University, Melbourne, Australia."), [Julie R Boiko](https://pubmed.ncbi.nlm.nih.gov/?term=Boiko+JR&cauthor_id=42379250)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-3 "Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-4 "Department of Pediatrics, University of Washington, Seattle, WA."), [Daniel C Jones](https://pubmed.ncbi.nlm.nih.gov/?term=Jones+DC&cauthor_id=42379250)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-5 "Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA."), [Daniel Wong](https://pubmed.ncbi.nlm.nih.gov/?term=Wong+D&cauthor_id=42379250)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-1 "Clinical Haematology, Alfred Health, Melbourne, Australia.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-2 "Australian Centre for Blood Diseases, Monash University, Melbourne, Australia."), [Tiffany Khong](https://pubmed.ncbi.nlm.nih.gov/?term=Khong+T&cauthor_id=42379250)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-1 "Clinical Haematology, Alfred Health, Melbourne, Australia.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-2 "Australian Centre for Blood Diseases, Monash University, Melbourne, Australia."), [Sridurga Mithraprabhu](https://pubmed.ncbi.nlm.nih.gov/?term=Mithraprabhu+S&cauthor_id=42379250)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-1 "Clinical Haematology, Alfred Health, Melbourne, Australia.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-2 "Australian Centre for Blood Diseases, Monash University, Melbourne, Australia."), [Kathleen S Ensbey](https://pubmed.ncbi.nlm.nih.gov/?term=Ensbey+KS&cauthor_id=42379250)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-3 "Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA."), [Anna E Elz](https://pubmed.ncbi.nlm.nih.gov/?term=Elz+AE&cauthor_id=42379250)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-6 "Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA."), [Evan W Newell](https://pubmed.ncbi.nlm.nih.gov/?term=Newell+EW&cauthor_id=42379250)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-5 "Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-6 "Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA."), [Andrew Spencer](https://pubmed.ncbi.nlm.nih.gov/?term=Spencer+A&cauthor_id=42379250)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-1 "Clinical Haematology, Alfred Health, Melbourne, Australia.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-2 "Australian Centre for Blood Diseases, Monash University, Melbourne, Australia."), [Geoffrey R Hill](https://pubmed.ncbi.nlm.nih.gov/?term=Hill+GR&cauthor_id=42379250)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-3 "Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-6 "Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-7 "Faculty of Medicine Nursing and Health Sciences, School of Biomedical Sciences, Monash University, Melbourne, Australia.")[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#full-view-affiliation-8 "Department of Medical Oncology, University of Washington, Seattle, WA.") Affiliations Expand ### Affiliations * 1 Clinical Haematology, Alfred Health, Melbourne, Australia. * 2 Australian Centre for Blood Diseases, Monash University, Melbourne, Australia. * 3 Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA. * 4 Department of Pediatrics, University of Washington, Seattle, WA. * 5 Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA. * 6 Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA. * 7 Faculty of Medicine Nursing and Health Sciences, School of Biomedical Sciences, Monash University, Melbourne, Australia. * 8 Department of Medical Oncology, University of Washington, Seattle, WA. * PMID: **42379250** * PMCID: [ PMC13584121 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13584121/) * DOI: [ 10.1182/bloodadvances.2026020500 ](https://doi.org/10.1182/bloodadvances.2026020500) Item in Clipboard # Spatial transcriptomics identifies a suppressive, T-cell-excluded tumor microenvironment in extramedullary myeloma Nicholas E Bingham et al. Blood Adv. 2026. Show details Display options Display options Format Abstract PubMed PMID Blood Adv Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Blood+Adv%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Blood+Adv%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42379250/) . 2026 Sep 22;10(18):6221-6235. doi: 10.1182/bloodadvances.2026020500. ### Authors [Nicholas E Bingham](https://pubmed.ncbi.nlm.nih.gov/?term=Bingham+NE&cauthor_id=42379250)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-1 "Clinical Haematology, Alfred Health, Melbourne, Australia.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-2 "Australian Centre for Blood Diseases, Monash University, Melbourne, Australia."), [Julie R Boiko](https://pubmed.ncbi.nlm.nih.gov/?term=Boiko+JR&cauthor_id=42379250)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-3 "Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-4 "Department of Pediatrics, University of Washington, Seattle, WA."), [Daniel C Jones](https://pubmed.ncbi.nlm.nih.gov/?term=Jones+DC&cauthor_id=42379250)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-5 "Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA."), [Daniel Wong](https://pubmed.ncbi.nlm.nih.gov/?term=Wong+D&cauthor_id=42379250)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-1 "Clinical Haematology, Alfred Health, Melbourne, Australia.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-2 "Australian Centre for Blood Diseases, Monash University, Melbourne, Australia."), [Tiffany Khong](https://pubmed.ncbi.nlm.nih.gov/?term=Khong+T&cauthor_id=42379250)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-1 "Clinical Haematology, Alfred Health, Melbourne, Australia.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-2 "Australian Centre for Blood Diseases, Monash University, Melbourne, Australia."), [Sridurga Mithraprabhu](https://pubmed.ncbi.nlm.nih.gov/?term=Mithraprabhu+S&cauthor_id=42379250)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-1 "Clinical Haematology, Alfred Health, Melbourne, Australia.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-2 "Australian Centre for Blood Diseases, Monash University, Melbourne, Australia."), [Kathleen S Ensbey](https://pubmed.ncbi.nlm.nih.gov/?term=Ensbey+KS&cauthor_id=42379250)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-3 "Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA."), [Anna E Elz](https://pubmed.ncbi.nlm.nih.gov/?term=Elz+AE&cauthor_id=42379250)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-6 "Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA."), [Evan W Newell](https://pubmed.ncbi.nlm.nih.gov/?term=Newell+EW&cauthor_id=42379250)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-5 "Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-6 "Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA."), [Andrew Spencer](https://pubmed.ncbi.nlm.nih.gov/?term=Spencer+A&cauthor_id=42379250)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-1 "Clinical Haematology, Alfred Health, Melbourne, Australia.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-2 "Australian Centre for Blood Diseases, Monash University, Melbourne, Australia."), [Geoffrey R Hill](https://pubmed.ncbi.nlm.nih.gov/?term=Hill+GR&cauthor_id=42379250)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-3 "Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-6 "Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-7 "Faculty of Medicine Nursing and Health Sciences, School of Biomedical Sciences, Monash University, Melbourne, Australia.")[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42379250/#short-view-affiliation-8 "Department of Medical Oncology, University of Washington, Seattle, WA.") ### Affiliations * 1 Clinical Haematology, Alfred Health, Melbourne, Australia. * 2 Australian Centre for Blood Diseases, Monash University, Melbourne, Australia. * 3 Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA. * 4 Department of Pediatrics, University of Washington, Seattle, WA. * 5 Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA. * 6 Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA. * 7 Faculty of Medicine Nursing and Health Sciences, School of Biomedical Sciences, Monash University, Melbourne, Australia. * 8 Department of Medical Oncology, University of Washington, Seattle, WA. * PMID: **42379250** * PMCID: [ PMC13584121 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13584121/) * DOI: [ 10.1182/bloodadvances.2026020500 ](https://doi.org/10.1182/bloodadvances.2026020500) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Extramedullary disease (EMD) in multiple myeloma (MM) is associated with poor outcomes because of aggressive disease kinetics and therapy resistance. The bone marrow (BM) tumor microenvironment (TME) promotes cell survival and drug resistance in marrow-restricted MM, but little is known about the TME in EMD. To characterize the tissue architecture of these tumors, we performed spatial transcriptomics on tumor biopsies. Similar to BM-restricted MM, we identified significant interpatient heterogeneity in plasma cell (PC) expression profiles, although still maintaining a characteristic PC transcriptome. The TME was dominated by macrophages with a suppressive "M2" phenotype. CD8+ T cells frequently expressed exhaustion markers LAG3 and TIGIT, consistent with a suppressive TME. We identified 3 recurrent TME niches based on immune cell composition: immune excluded, immune suppressed, and immune permissive. The immune-excluded niche comprised the bulk of tumors, reflecting spatial exclusion of immune cells. The suppressive extracellular matrix (ECM) from abundant tumor-associated fibroblasts in the immune-suppressive niche may further contribute to T-cell exclusion. Cell-cell interaction modeling revealed a complex, bidirectional network: PC modulated the TME through PGE2 and VEGFB while receiving canonical prosurvival signals through CD38, CXCR4, and BCMA. Notably, TME cells, particularly fibroblasts and macrophages, are predicted to collectively promote the suppressive macrophage phenotype and fibrotic ECM, reinforcing an immunosuppressive milieu that supports local disease progression. These findings reveal the spatial organization of EMD, highlighting niche substitution rather than niche independence, and identify clinically tractable microenvironmental niches and signaling networks in this high-risk myeloma subset. © 2026 American Society of Hemato
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