Immune profile in the peripheral blood (pb) of patients with follicular lymphoma (fl) at diagnosis and upon relapse

Introduction: FL is characterized by a heterogeneous clinical course. The biologic importance of the tumour microenvironment in FL pathogenesis is well established. However, detailed information on the immune profile in PB has not been previously investigated, which becomes very relevant in the current era of the immunotherapy. The aim of this study was to characterise the PB immune profile of FL patients at diagnosis, first relapse (R1) and subsequent relapses (>R2) and compare them with healthy controls. Moreover, R1 was also analysed according to histological transformation (HT) and POD24 status. Methods: We collected PB samples of FL patients at diagnosis (n = 42), R1 (n = 22) and >R2 (n = 16) from April 2019 to August 2022 (median age at diagnosis: 65 years [30–82]; 22M/20F). 15 PB samples from healthy donors were also obtained (median age: 31 years [28–65]; 5M/10F). All individuals signed informed consent. The identification of major subsets of T-cells, B-cells, NK cells, monocytes, neutrophils, eosinophils, basophils, dendritic cells (DC) and myeloid suppressor cells (MSC) was performed by multiparameter flow cytometry. Euroflow methodology was used to set up the Omnicyt™ flow cytometer and acquired at least 150.000 events. All data were analysed using Infinicyt™ software version 2.0 (Cytognos, Salamanca, Spain). Results: Compared with healthy controls, FL patients showed a lower CD4+/CD8+ ratio due to an increase in CD8+ lymphocytes and a decrease in total CD4+ lymphocytes. In addition, FL patients had a significantly lower percentage of naïve T lymphocytes, a higher percentage of effector memory and effector lymphocytes, both CD4+ and CD8+. Of note, regulatory T lymphocytes (Treg) and Th1 cells were increased in FL patients, while NK-cells were diminished. Interestingly, differences in DC and MSC were also found between healthy controls and FL patients (Figure). These differences remained when comparing the immune populations between diagnosis and relapse and deepened with each relapse. No differences were observed between groups in the percentage of neutrophils, monocytes, eosinophils, or total B lymphocytes. A subanalysis performed in R1 samples according to HT and POD24 status revealed that HT-R1 presented significantly a smaller CD8+ central memory population compared with non HT-R1. POD24 patients displayed a lower CD4+/CD8+ ratio and a higher proportion of Th1 cells (p < 0.05). In both adverse prognostic groups, the percentage of myeloid DC and neutrophils was significantly lower. The research was funded by: This study has been funded by Instituto de Salud Carlos III (ISCIII) through the projects PI19/00887 to A.L.-G. and E.G., and PI19/00925 to L.M. Andrea Rivero was supported by a grant from Hospital Clinic de Barcelona during the conduct of the study. Keywords: indolent non-Hodgkin lymphoma, microenvironment No conflicts of interests pertinent to the abstract.