ArticleBlood cancer journal2021
Lack of intrafollicular memory CD4 + T cells is predictive of early clinical failure in newly diagnosed follicular lymphoma.
Article in Blood cancer journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 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
- Dual targeting PD-L1 and 4-1BB to overcome dendritic cell-mediated lenalidomide resistance in follicular lymphoma.Signal transduction and targeted therapy · 2025Trial
- Trial
- Dysregulated KMT2D mutant targeting immunogenic rewiring to overcome epigenetic entropy promotes follicular lymphomagenesis.Experimental hematology & oncology · 2026Article
- Malignant B-cell States Orchestrate Spatially Organized Immune Ecosystems in B-cell Lymphomas.Research square · 2026Article
- Development and validation of a gene expression signature to predict early events in patients with follicular lymphoma.Blood advances · 2025Article
- IRF4 Promotes Immune Evasion and Shapes the Tumor Microenvironment in Follicular Lymphoma.Blood cancer discovery · 2025Article
- Subsets of follicular lymphoma 3B have divergent outcomes: results from the prospective multicenter MER and LEO cohorts.Blood cancer journal · 2025Article
- Deep immunophenotypic dissection and clinical impact of T cells in the follicular lymphoma microenvironment.Haematologica · 2025Article
- Exploratory Study to Evaluate the Impact of Interim PET/CT Assessment in First-Line Follicular Lymphoma.Cancers · 2025Article
- Treatment patterns and outcomes in follicular lymphoma with POD24: an analysis from the LEO Consortium.Blood advances · 2025Article
- Integration of PET/CT parameters and a clinical variable to predict the risk of progression of disease within 24 months (POD24) in follicular lymphoma.Quantitative imaging in medicine and surgery · 2025Article
- A Phase I Clinical Trial Adding OX40 Agonism to In Situ Therapeutic Cancer Vaccination in Patients with Low-Grade B-cell Lymphoma Highlights Challenges in Translation from Mouse to Human Studies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- BNT162b2 mRNA vaccination affects the gut microbiome composition of patients with follicular lymphoma and chronic lymphocytic leukemia.Biomarker research · 2025Article
- A novel case of glial transdifferentiation in renal medullary carcinoma brain metastasis.Acta neuropathologica communications · 2025Article
- Histopathology-based protein multiplex generation using deep learning.Nature machine intelligence · 2025Article
- Follicular lymphoma research: an open dialogue for a collaborative roadmap.Histopathology · 2025Review
- The POD24 challenge: where do we go from here for early progressors?Hematology. American Society of Hematology. Education Program · 2024Review
- Changes of T cell subsets across treatments associated with prognosis in newly diagnosed follicular lymphoma.Scientific reports · 2024Article
- Impact of the Immune Landscape in Follicular Lymphoma: Insights into Histological Transformation in the Rituximab Era.Cancers · 2024Article
Corrections and comments
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Authors and funding
25 authors at 6 institutions in 3 countries.
Funding
Abstract
Despite a characteristic indolent course, a substantial subset of follicular lymphoma (FL) patients has an early relapse with a poor outcome. Cells in the microenvironment may be a key contributor to treatment failure. We used a discovery and validation study design to identify microenvironmental determinants of early failure and then integrated these results into the FLIPI. In total, 496 newly diagnosed FL grade 1-3 A patients who were prospectively enrolled into the MER cohort from 2002 to 2012 were evaluated. Tissue microarrays were stained for CD4, CD8, FOXP3, CD32b, CD14, CD68, CD70, SIRP-α, TIM3, PD-1, and PD-L1. Early failure was defined as failing to achieve event-free survival at 24 months (EFS24) in immunochemotherapy-treated patients and EFS12 in all others. CyTOF and CODEX analysis were performed to characterize intratumoral immunophenotypes. Lack of intrafollicular CD4 expression was the only predictor of early failure that replicated with a pooled OR 2.37 (95%CI 1.48-3.79). We next developed a bio-clinical risk model (BioFLIPI), where lack of CD4 intrafollicular expression moved patients up one FLIPI risk group, adding a new fourth high-risk group. Compared with BioFLIPI score of 1, patients with a score of 2 (OR 2.17; 95% CI 1.08-4.69), 3 (OR 3.53; 95% CI 1.78-7.54), and 4 (OR 8.92; 95% CI 4.00-21.1) had increasing risk of early failure. The favorable intrafollicular CD4 T cells were identified as activated central memory T cells, whose prognostic value was independent from genetic features. In conclusion, lack of intrafollicular CD4 expression predicts early failure in FL and combined with FLIPI improves identification of high-risk patients; however, independent validation is warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.