ArticleJournal of clinical and experimental hematopathology : JCEH2019
High TNFRSF14 and low BTLA are associated with poor prognosis in Follicular Lymphoma and in Diffuse Large B-cell Lymphoma transformation.
Article in Journal of clinical and experimental hematopathology : JCEH, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
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Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Molecular Biomarkers in Prediction of High-Grade Transformation and Outcome in Patients with Follicular Lymphoma: A Comprehensive Systemic Review.International journal of molecular sciences · 2024Pooled it
- Prognostic role of regulatory T cells in lymphoma: a systematic review and meta-analysis.Journal of cancer research and clinical oncology · 2020Pooled it
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- Intraepithelial Lymphocytes and LAIR1 Expression in Celiac Disease.Biomedicines · 2025Article
- Molecular Mechanisms in the Transformation from Indolent to Aggressive B Cell Malignancies.Cancers · 2025Review
- Immune dysregulation in COVID-19 induced ARDS in kidney transplant recipients revealed by single-cell RNA sequencing.Scientific reports · 2025Article
- Identification of Plasma Protein Biomarkers and Drug Targets for Hematologic Malignancies by Proteome-wide Mendelian Randomization.Journal of Cancer · 2025Article
- HVEM in acute lymphocytic leukemia facilitates tumour immune escape by inhibiting CD8Cellular oncology (Dordrecht, Netherlands) · 2024Article
- The role of the BTLA-HVEM complex in the pathogenesis of breast cancer.Breast cancer (Tokyo, Japan) · 2024Review
- BTLA biology in cancer: from bench discoveries to clinical potentials.Biomarker research · 2024Review
- Patient-derived lymphoma spheroids integrating immune tumor microenvironment as preclinical follicular lymphoma models for personalized medicine.Journal for immunotherapy of cancer · 2023Article
- Predictive value of DOT1L mutations for clinical outcomes in non-small-cell lung cancer patients receiving immune checkpoint inhibitor therapy.Clinical and translational medicine · 2023Article
- The pathobiology of follicular lymphoma.Journal of clinical and experimental hematopathology : JCEH · 2023Article
- Beyond the anti-PD-1/PD-L1 era: promising role of the BTLA/HVEM axis as a future target for cancer immunotherapy.Molecular cancer · 2023Review
- BTLA dysregulation correlates with poor outcome and diminished T cell-mediated antitumor responses in chronic lymphocytic leukemia.Cancer immunology, immunotherapy : CII · 2023Article
- Mutational Profile and Pathological Features of a Case of Interleukin-10 and RGS1-Positive Spindle Cell Variant Diffuse Large B-Cell Lymphoma.Hematology reports · 2023Article
- The Immunology of DLBCL.Cancers · 2023Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The microenvironment influences the behavior of follicular lymphoma (FL) but the specific roles of the immunomodulatory BTLA and TNFRSF14 (HVEM) are unknown. Therefore, we examined their immunohistochemical expression in the intrafollicular, interfollicular and total histological compartments in 106 FL cases (57M/49F; median age 57-years), and in nine relapsed-FL with transformation to DLBCL (tFL). BTLA expression pattern was of follicular T-helper cells (TFH) in the intrafollicular and of T-cells in the interfollicular compartments. The mantle zones were BTLA+ in 35.6% of the cases with similar distribution of IgD. TNFRSF14 expression pattern was of neoplastic B lymphocytes (centroblasts) and "tingible body macrophages". At diagnosis, the averages of total BTLA and TNFRSF14-positive cells were 19.2%±12.4STD (range, 0.6%-58.2%) and 46.7 cells/HPF (1-286.5), respectively. No differences were seen between low-grade vs. high-grade FL but tFL was characterized by low BTLA and high TNFRSF14 expression. High BTLA correlated with good overall survival (OS) (total-BTLA, Hazard Risk=0.479, P=0.022) and with high PD-1 and FOXP3+Tregs. High TNFRSF14 correlated with poor OS and progression-free survival (PFS) (total-TNFRSF14, HR=3.9 and 3.2, respectively, P<0.0001), with unfavorable clinical variables and higher risk of transformation (OR=5.3). Multivariate analysis including BTLA, TNFRSF14 and FLIPI showed that TNFRSF14 and FLIPI maintained prognostic value for OS and TNFRSF14 for PFS. In the GSE16131 FL series, high TNFRSF14 gene expression correlated with worse prognosis and GSEA showed that NFkB pathway was associated with the "High-TNFRSF14/dead-phenotype".In conclusion, the BTLA-TNFRSF14 immune modulation pathway seems to play a role in the pathobiology and prognosis of FL.
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