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
Recommended Citation
Li, Xubin; Singhal, Kartik; Deng, Qing; et al., "Large B Cell Lymphoma Microenvironment Archetype Profiles" (2025). Faculty, Staff and Student Publications. 6852.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6852
Graphical Abstract
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Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons