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
PubMed

Insights

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.

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.

Related Concept Videos

B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
16.1K
Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
8.5K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.6K
Lymphoid Cells and Tissues01:18

Lymphoid Cells and Tissues

Lymphoid cells and tissues are integral to the immune system, which is crucial in maintaining our body's defense against harmful pathogens. They form the building blocks of lymphoid organs, which include the spleen, thymus, and lymph nodes.
Lymphoid cells consist of various types of immune system cells. These include B and T lymphocytes, which are responsible for producing antibodies and killing infected cells, respectively. Dendritic cells act as messengers between the innate and adaptive...
2.9K
Primary Lymphoid Organs01:16

Primary Lymphoid Organs

Primary lymphoid organs are pivotal in the formation, development, and maturation of lymphocytes, the white blood cells that serve as the backbone of our immune system. This crucial function underscores their fundamental role in maintaining our overall health and immunity. The two primary lymphoid organs of prime importance are the red bone marrow and the thymus.
The red bone marrow is a soft, spongy tissue nestled in the interior of long bones such as the humerus and femur. It is the site...
14.7K
Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
1.4K