LymphoMAPs: Decoding the Lymphoma Microenvironment

In an interview, Michael Green, PhD, associate professor of lymphoma/myeloma at The University of Texas MD Anderson Cancer Center in Houston, TX, discusses a novel method of identifying B-cell lymphoma traits called "lymphoMAPs" to assess response to chimeric antigen receptor (CAR) T-cell therapy.

Previous methods of molecularly characterizing lymphoma samples have primarily focused on the tumor B cells themselves. About 25 years ago, this was through cellular origin subtypes as a transcriptional program of the tumor cells, categorizing them into 2 groups. More recently, genetic classifiers have emerged, placing lymphomas into 5 or 6 different categories based on somatic mutations.

LymphoMAPs differ from these approaches because they entirely focused on the tumor microenvironment, or the the nontumor component of lymphomas. The tumor microenvironment includes lymphoid cells like T cells and NK cells, myeloid cells, and importantly, the endothelial and stromal cell compartments.

"In the past, we've missed these in our profiling efforts because we primarily used single-cell suspensions, which depleted these components," Green explained.

LymphoMAPS accounts for all cell types that are not the tumor and identifies reproducible patterns in how these are assembled into archetypical patterns across patients. Green and his fellow researchers discovered 3 major archetypes:

1. Fibroblast and Macrophage (F-Mac): This archetype is relatively depleted of T and NK cells. Instead, it's characterized by high frequencies of cancer-associated fibroblasts and tumor-associated macrophages.
2. Lymph Node and T-Exhausted Archetype: This archetype has high frequencies of T cells.
   • The lymph node archetype is named as such because it's partly characterized by a high frequency of architectural cells typically found within the lymph node, such as follicular dendritic cells and marginal zone reticular cells. These provide supportive cytokine help for the T cells. The T cells, which are more CD4-biased, exhibit healthier, more naive, and memory phenotypes. We call this a healthy T-cell-rich microenvironment.
   • The T-Exhausted archetype is also T-cell-rich, but it's not a healthy microenvironment. It lacks the architectural cells that provide supportive cytokines and instead has high frequencies of activated macrophages that drive T-cell exhaustion. The T-cell compartment in this archetype is CD8-biased, with cytotoxic phenotypes and phenotypes reflective of T-cell exhaustion.

REFERENCE:

Li X, Singhal K, Deng Q, et al. Large B cell lymphoma microenvironment archetype profiles. Canc Cell. Published online June 18, 2025. DOI: 10.1016/j.ccell.2025.06.002