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Large B cell lymphoma microenvironment archetype profiles.

Xubin Li1, Kartik Singhal2, Qing Deng3

  • 1Department of Lymphoma and Myeloma, University of Texas (UT) MD Anderson Cancer Center, Houston, TX, USA; Lymphoid Malignancies Program, UT MD Anderson Cancer Center, Houston, TX, USA.

Cancer Cell
|September 8, 2025
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Summary
This summary is machine-generated.

This study reveals distinct lymphoma microenvironment archetypes (LymphoMAPs) in large B cell lymphomas (LBCL). These archetypes, defined by cell compositions, impact T cell interactions and predict outcomes in chimeric antigen receptor (CAR) T cell therapy.

Keywords:
CAR T celllymphomamicroenvironmentsingle cell RNA sequencing

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Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Large B cell lymphomas (LBCL) are heterogeneous lymphoid malignancies.
  • Tumor microenvironments significantly influence LBCL pathogenesis and progression.
  • Understanding cellular composition is crucial for targeted therapies.

Purpose of the Study:

  • To comprehensively characterize cellular diversity within LBCL tumors.
  • To identify recurring patterns of cell co-occurrence, termed lymphoma microenvironment archetype profiles (LymphoMAPs).
  • To investigate the relationship between LymphoMAPs, cell-cell communication, and clinical outcomes, particularly following CAR T cell therapy.

Main Methods:

  • Single-nucleus multiome profiling was performed on 232 tumor and control biopsies.
  • Analysis focused on lymphoid, myeloid, and non-hematopoietic cell compartments.
  • Lymphoma microenvironment archetypes (LymphoMAPs) were defined based on cell subset frequencies.

Main Results:

  • Three stereotypical LymphoMAPs were identified: FMAC (fibroblasts, macrophages), LN (lymph node architecture), and TEX (exhausted T cells).
  • Distinct cell-cell communication patterns were associated with each LymphoMAP, influencing T cell exclusion, support, or suppression.
  • LymphoMAPs demonstrated significant associations with clinical outcomes after CD19 CAR T cell therapy.

Conclusions:

  • LBCL tumor microenvironments exhibit distinct, reproducible archetypes (LymphoMAPs).
  • These archetypes are shaped by specific cell-cell communication networks.
  • LymphoMAPs serve as predictive biomarkers for patient response to CAR T cell therapy in LBCL.