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High inter-follicular spatial co-localization of CD8+FOXP3+ with CD4+CD8+ cells predicts favorable outcome in follicular lymphoma

Hagos, Yeman B; Akarca, Ayse U; Ramsay, Alan; Rossi, Riccardo L; Pomplun, Sabine; Ngai, Victoria; Moioli, Alessia; ... Marafioti, Teresa; + view all (2022) High inter-follicular spatial co-localization of CD8+FOXP3+ with CD4+CD8+ cells predicts favorable outcome in follicular lymphoma. Hematological Oncology 10.1002/hon.3003. (In press). Green open access

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Abstract

The spatial architecture of the lymphoid tissue in follicular lymphoma (FL) presents unique challenges to studying its immune microenvironment. We investigated the spatial interplay of T cells, macrophages, myeloid cells and natural killer T cells using multispectral immunofluorescence images of diagnostic biopsies of 32 patients. A deep learning-based image analysis pipeline was tailored to the needs of follicular lymphoma spatial histology research, enabling the identification of different immune cells within and outside neoplastic follicles. We analyzed the density and spatial co-localization of immune cells in the inter-follicular and intra-follicular regions of follicular lymphoma. Low inter-follicular density of CD8+FOXP3+ cells and co-localization of CD8+FOXP3+ with CD4+CD8+ cells were significantly associated with relapse (p = 0.0057 and p = 0.0019, respectively) and shorter time to progression after first-line treatment (Logrank p = 0.0097 and log-rank p = 0.0093, respectively). A low inter-follicular density of CD8+FOXP3+ cells is associated with increased risk of relapse independent of follicular lymphoma international prognostic index (FLIPI) (p = 0.038, Hazard ratio (HR) = 0.42 [0.19, 0.95], but not independent of co-localization of CD8+FOXP3+ with CD4+CD8+ cells (p = 0.43). Co-localization of CD8+FOXP3+ with CD4+CD8+ cells is predictors of time to relapse independent of the FLIPI score and density of CD8+FOXP3+ cells (p = 0.027, HR = 0.0019 [7.19 × 10−6, 0.49], This suggests a potential role of inter-follicular CD8+FOXP3+ and CD4+CD8+ cells in the disease progression of FL, warranting further validation on larger patient cohorts.

Type: Article
Title: High inter-follicular spatial co-localization of CD8+FOXP3+ with CD4+CD8+ cells predicts favorable outcome in follicular lymphoma
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/hon.3003
Publisher version: https://doi.org/10.1002/hon.3003
Language: English
Additional information: Copyright © 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Keywords: CD4+CD8+, CD8+FOXP3+, deep learning, follicular lymphoma, image analysis, multispectral immunofluorescence
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
URI: https://discovery.ucl.ac.uk/id/eprint/10149261
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