17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Abstract

Background: Cancer is a recognized condition of secondary immunosuppression. Lymphoma patients often show a decrease in absolute lymphocyte counts and in peripheral blood gamma-globulin levels. However, less is known about how NK cells are altered in lymphoma patients. The aim of this study was to evaluate the patterns of circulating NK cell dysfunction in lymphoma patients. Methods: We performed a cross-sectional study of patients with a recent diagnosis of nodal lymphoproliferative disorder. Patients with active anticancer treatment or steroid use were excluded. Peripheral blood samples in EDTA were analyzed by multicolor flow cytometry. A custom panel of 30 markers was applied to all samples to test for major subpopulations, maturation, and functional markers. Results were compared to healthy controls. Clinical data were obtained from the electronic database. This study was approved by the institutional IRB and Clinical Ethics Committee. Results: A total of 30 patients were examined between October 2021 and November 2022. The median age was 62 years (range 15–88) and 45.7% were female (16). Patients had the following subtypes: large B-cell lymphoma (LBCL; 9), follicular lymphoma (FL; 9), Hodgkin lymphoma (HL; 5), mantle cell lymphoma (MCL; 4), marginal zone lymphoma (MZL; 2), Waldenström macroglobulinemia (WM; 1). Most patients had advanced stage disease (20). Compared to healthy controls (n = 10), lymphoma patients showed a significant decrease in absolute NK cell counts (ANKC, 319.7 vs. 131.1 cells/mm3; p < 0.0001). MCL patients had the lowest ANKC (68.8) and Hodgkin patients the highest (165.6). Advanced stage disease correlated with lower ANKC compared to localized disease (99.85 vs. 148.9; p = ns). The pattern of maturation was altered in lymphoma patients compared to controls (p = 0.0092). Patients had a higher proportion of immature CD56-bright NK cells (4.97% vs. 2.88%) and lower levels of CD16 expression in the mature CD56-dim subpopulation (68.12% vs. 85.94%). Lymphoma patients also showed dysfunctional expression of receptors and activation markers (Figure). There was a significant increase in the levels of FAS-L, IFNg, CD49b, CD57, CD96, and CD107a, while the levels of TIGIT and NKG2D were significantly decreased. Differences in the expression of immune checkpoints (PD-1, LAG-3, TIM-3), as well as additional activating, inhibitory, and chemokine receptors were not significant. 22 of 30 patients (73.3%) achieved a complete response. All patients with ANKC above 135 cells/mm3 at diagnosis achieved sustained complete remission. The research was funded by: Fondecyt 11200805 Clínica Alemana de Santiago ID1025 Keyword: diagnostic and prognostic biomarkers No conflicts of interests pertinent to the abstract.