Abstract

BackgroundRegulatory immune cells may modulate the lymphoma microenvironment and are of great interest due to the increasing prevalence of treatment with immunotherapies in lymphoma patients. The aim was to explore the composition of different immune regulatory cell subsets in the peripheral blood of newly diagnosed lymphoma patients in relation to treatment outcome.MethodsForty-three newly diagnosed patients with lymphoma were included in the study; 24 with high-grade B-cell lymphoma (HGBCL) and 19 with classical Hodgkin lymphoma (cHL). Peripheral blood was prospectively collected and immune regulatory cells were identified by multi-color flow cytometry and analyzed in relation to healthy blood donors and clinical characteristics and outcome.ResultsThe percentage of CD3-positive T-cells was lower (p = 0.03) in the peripheral blood of lymphoma patients at diagnosis compared to healthy blood donors regardless of lymphoma subtype, although statistically, neither the percentage of monocytes (p = 0.2) nor the T-cell/monocyte ratio (p = 0.055) differed significantly. A significant decrease in the percentage of a subset of regulatory NK cells (CD7+/CD3−/CD56bright/CD16dim/−) was identified in the peripheral blood of lymphoma patients compared to healthy blood donors (p = 0.003). Lymphoma patients also had more granulocytic myeloid-derived suppressor cells (MDSCs) (p = 0.003) compared to healthy blood donors, whereas monocytic MDSCs did not differ significantly (p = 0.07). A superior disease-free survival was observed for cHL patients who had an increase in the percentage of granulocytic MDSCs (p = 0.04).ConclusionsAn altered profile of immune cells in the peripheral blood with a decrease in T-cells and regulatory NK-cells was observed in newly diagnosed lymphoma patients. CHL patients with higher percentages of regulatory NK cells and higher percentages of granulocytic MDSCs might have a better outcome, although the number of patients was low.

Highlights

  • Regulatory immune cells may modulate the lymphoma microenvironment and are of great interest due to the increasing prevalence of treatment with immunotherapies in lymphoma patients

  • Immune suppression has long been associated with classical Hodgkin lymphoma where severe lymphopenia is included in the International Prognostic Score (IPS) [1] probably reflecting impaired host immunity, and an increase in activated (CD4+/CD25+) T-cells has been observed in the peripheral blood of long-term

  • In this study we show a significantly lower percentage of regulatory NK cells in newly diagnosed lymphoma patients, both classical Hodgkin lymphoma (cHL) and high-grade Bcell lymphoma (HGBCL) compared to healthy blood donors

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Summary

Introduction

Regulatory immune cells may modulate the lymphoma microenvironment and are of great interest due to the increasing prevalence of treatment with immunotherapies in lymphoma patients. The aim was to explore the composition of different immune regulatory cell subsets in the peripheral blood of newly diagnosed lymphoma patients in relation to treatment outcome. In cHL, a correlation with poor prognostic markers was observed [9] but the role of T regulatory cells in lymphoma patients is not fully elucidated. Immune cells in the peripheral blood of lymphoma patients have been subject to attention lately due to the possible relation to tumor microenvironment and immune status. Important immune regulatory mechanisms need to be better defined in order to be targeted with immunotherapies like those directed towards the programmed death receptor 1 (PD-1) immune checkpoint pathway. Targeting the PD-1/PD-Ll interactions influences T-cells, and NK cells, monocytes and myeloid-derived suppressor cells (MDSCs) and it might be important to evaluate all these cell populations in order to identify patients who might respond favorably to PD-1 pathway inhibitors [11]

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