DOI: 10.6084/m9.figshare.23497445.v1
title: 2023_TumedeiEtAl_FollicularLymphoma _Scripts_Tables_SupFig6

description: COLLECTION ITEM: Article data <br> PROJECT TITLE: 2023_TumedeiEtAl_FollicularLymphoma <br> ARTICLE (when using these files, please, cite the following article): M.M. Tumedei, F. Piccinini, I. Azzali, F. Pirini, S. Bravaccini, S. De Matteis, C. Agostinelli, G. Castellani, M. Zanoni, M. Cortesi, V. Barbara, B.E. Leone, S. Righi, A. Gazzola, B. Casadei, G. Davide, L. Calzari, F. Limarzi, E. Sabattini, A. Pession, M. Tazzari, C. Bertuzzi, Follicular Lymphoma Microenvironment Traits Associated with Event-Free Survival, International Journal of Molecular Sciences, 2023. <br> DESCRIPTION OF THE FILES IN THE COLLECTION: Files, images and data used in the above mentioned scientific work. <br> MAIN CONTACT FOR THIS WORK: Dr. Marcella Tazzari, PhD, IRST IRCCS Meldola Italy. Email: marcella.tazzari@irst.emr.it <br> MAIN AFFILIATION FOR THIS WORK: IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola (FC), Italy. <br> KEYWORDS: Follicular Lymphoma immunohistochemistry tumor-associated macrophages progressive disease tumor microenvironment digital pathology <br> ABSTRACT OF THE ARTICLE: The majority of patients with Follicular Lymphoma (FL) experience subsequent phases of remission and relapse, making the disease “virtually” incurable. To predict the outcome of FL patients at diagnosis, various clinical-based prognostic scores have been proposed; nonetheless, they continue to fail for a subset of patients. Gene expression profiling has highlighted the pivotal role of the tumor microenvironment (TME) in the FL prognosis; nevertheless, there is still a need to standardize the assessment of immune-infiltrating cells for the prognostic classification of patients with early or late progressing disease. We studied a retrospective cohort of 49 FL lymph node biopsies at the time of the initial diagnosis using pathologist-guided analysis on whole slide images, and we characterized the immune repertoire for both quantity and distribution (intrafollicular, IF and extrafollicular, EF) of cell subsets in relation to clinical outcome. We looked for the natural killer (CD56), T lymphocyte (CD8, CD4, PD1) and macrophage (CD68, CD163, MA4A4A)-associated markers. High CD163/CD8 EF ratios and high CD56/MS4A4A EF ratios, according to Kaplan–Meier estimates were linked with shorter EFS (event-free survival), with the former being the only one associated with POD24. In contrast to IF CD68+ cells, which represent a more homogeneous population, higher in non-progressing patients, EF CD68+ macrophages did not stratify according to survival. We also identify distinctive MS4A4A+CD163-macrophage populations with different prognostic weights. Enlarging the macrophage characterization and combining it with a lymphoid marker in the rituximab era, in our opinion, may enable prognostic stratification for low-/high-grade FL patients beyond POD24. These findings warrant validation across larger FL cohorts. <br> COPYRIGHT: * Copyright (c) 2023, * IRST IRCCS Meldola, Italy * All rights reserved. * This material is free; you can redistribute it and/or modify it under the terms of the CC BY 4.0. * This material is distributed WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.