Journal article
Lack of intrafollicular memory CD4 + T cells is predictive of early clinical failure in newly diagnosed follicular lymphoma
Blood cancer journal (New York), Vol.11(7), pp.1-11
07/01/2021
DOI: 10.1038/s41408-021-00521-4
PMCID: PMC8282842
PMID: 34267181
Abstract
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.
Details
- Title: Subtitle
- Lack of intrafollicular memory CD4 + T cells is predictive of early clinical failure in newly diagnosed follicular lymphoma
- Creators
- Patrizia Mondello - Mayo ClinicAngelo Fama - Arcispedale Santa Maria NuovaMelissa C. Larson - Mayo ClinicAndrew L. Feldman - Mayo ClinicJose C. Villasboas - Mayo ClinicZhi-Zhang Yang - Mayo ClinicIlia Galkin - BostonGene, Waltham, MA, USA.Viktor Svelolkin - BostonGene, Waltham, MA, USA.Ekaterina Postovalova - BostonGene, Waltham, MA, USA.Alexander Bagaev - BostonGene, Waltham, MA, USA.Pavel Ovcharov - BostonGene, Waltham, MA, USA.Arina Varlamova - BostonGene, Waltham, MA, USA.Sarah Huet - Université Claude Bernard Lyon 1Bruno Tesson - Institut Carnot CALYM, Paris, France.Kaitlyn R. McGrath - Mayo ClinicSusan Slager - Mayo ClinicBrian K. Link - University of IowaSergei Syrbu - University of IowaAnne J. Novak - Mayo ClinicThomas M. Habermann - Mayo ClinicThomas E. Witzig - Mayo ClinicGrzegorz S. Nowakowski - Mayo ClinicGilles Salles - Université Claude Bernard Lyon 1James R. Cerhan - Mayo ClinicStephen M. Ansell - Mayo Clinic
- Resource Type
- Journal article
- Publication Details
- Blood cancer journal (New York), Vol.11(7), pp.1-11
- DOI
- 10.1038/s41408-021-00521-4
- PMID
- 34267181
- PMCID
- PMC8282842
- NLM abbreviation
- Blood Cancer J
- eISSN
- 2044-5385
- Publisher
- Nature Publishing Group
- Grant note
- DOI: 10.13039/100011541, name: U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute, award: P50 CA97274, U01 CA195568; name: U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute; DOI: 10.13039/100005189, name: Leukemia and Lymphoma Society
- Language
- English
- Date published
- 07/01/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Pathology; Internal Medicine
- Record Identifier
- 9984186423402771
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