Faculty, Staff and Student Publications

Language

English

Publication Date

7-14-2025

Journal

Cancer Cell

DOI

10.1016/j.ccell.2025.06.002

PMID

40920660

PMCID

PMC12417684

PubMedCentral® Posted Date

6-18-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Large B cell lymphomas (LBCL) are clinically and biologically heterogeneous lymphoid malignancies with complex microenvironments that are central to disease etiology. Here we have employed single-nucleus multiome profiling of 232 tumor and control biopsies to characterize diverse cell types and subsets that are present in LBCL tumors, effectively capturing the lymphoid, myeloid, and non-hematopoietic cell compartments. Cell subsets co-occurred in stereotypical Lymphoma Microenvironment Archetype Profiles (LymphoMAPs) defined by; (i) a sparsity of T cells and high frequencies of cancer-associated fibroblasts and tumor-associated macrophages [FMAC]; (ii) lymph node architectural cell types with naïve and memory T cells [LN]; or (iii) activated macrophages and exhausted CD8+ T cells [TEX]. Divergent patterns of cell-cell communication underpinned the transcriptional phenotypes of archetype-defining cell subsets resulting in exclusion, support or suppression of T cells, respectively. Consistent with this, LymphoMAPs were associated with significantly different clinical outcomes following CD19 chimeric antigen receptor (CAR) T cell therapy.

Keywords

Humans, Tumor Microenvironment, Lymphoma, Large B-Cell, Diffuse, CD8-Positive T-Lymphocytes, Tumor-Associated Macrophages, Immunotherapy, Adoptive, Male, Female, Lymph Nodes

Published Open-Access

yes

nihms-2088341-f0001.jpg (264 kB)
Graphical Abstract

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