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Researchers characterized the microenvironment of a nodal T cell lymphoma that is difficult to diagnose and treat
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The study identified CD40 as a potential biomarker associated with overall survival
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Future studies may look at targeting the CD40 pathway as a potential therapeutic target
ORLANDO, DECEMBER 7, 2025 - Researchers at The University of Texas MD Anderson Cancer Center have characterized the complex microenvironment in angioimmunoblastic T cell lymphoma (AITL), a type of nodal T cell lymphoma, and identified overexpression of the CD40 protein as a potential biomarker associated with improved overall survival (OS).
The study was led by Francisco Vega, M.D., Ph.D., professor of Hematopathology, and Tania Sainz, graduate research assistant. Pirmin Schlicke, Ph.D., postdoctoral fellow in Radiation Oncology, assisted with the digital analysis of CD40 expression. Sainz presented the study results today at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 555). All ASH content from MD Anderson can be found at MDAnderson.org/ASH.
“The discovery of CD40 overexpression as a potential biomarker gives us a new lens to assess patient risk and opens the door to therapeutic strategies that could improve outcomes for this challenging disease, especially since no biomarkers to predict OS are currently available,” Sainz said.
What is AITL and how does this study improve understanding of the disease?
AITL is a type of non-Hodgkin lymphoma that arises from T follicular helper (TFH) cells and involves the lymph nodes, bone marrow and, in some cases, the liver or spleen. AITL develops within a complex lymphoma microenvironment dominated by immune cells, with relatively few neoplastic TFH cells, often leading to delayed or incorrect diagnoses and poor therapeutic responses.
The researchers used single-cell RNA sequencing (scRNAseq) together with COMET, a sequential immunofluorescence assay. scRNAseq measures gene expression at the individual cell level, allowing for a detailed analysis of rare cell types and the ability to track immune cell evolution. COMET further supported the identification of cell type-specific markers within these samples. Through this approach, the researchers worked to uncover potential biomarkers within the complex AITL microenvironment.
What are the key findings of the study?
The researchers discovered that, in a subset of AITLs, malignant TFH cells showed increased expression of genes typically associated with regulatory T cells, such as FOXP3, suggesting that these cells may adopt a T follicular-regulatory program. An analysis of cells from 14 AITL lymph nodes and three reactive lymph nodes also presented two distinct microenvironments, both of which had elevated expression of the CD40 protein at specific locations. Further analysis showed that elevated CD40 also is seen in patient-derived xenograft lymphoma samples.
These findings suggest that malignant TFH cells in AITL have adaptative features that allow them to shift their phenotype. This biological variability may contribute to the diagnostic challenges seen in AITL. This is the first time that a T follicular-regulatory phenotype has been described, and it will now be important to determine the clinicopathologic features of these cases and how frequently this phenotype occurs.
Additionally, the overexpression of CD40 could be a potential biomarker to identify patient risk and improve treatment response monitoring. Further studies are needed to explore targeting the CD40 pathways as part of a potential therapeutic strategy.
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The study was supported by MD Anderson institutional funding. A full list of collaborating authors and their disclosures can be found with the abstract.