Oncotarget

Research Papers:

Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the peripheral blood of Hodgkin and non-Hodgkin lymphoma patients

Olivia Marini, Cecilia Spina, Elda Mimiola, Adriana Cassaro, Giovanni Malerba, Giuseppe Todeschini, Omar Perbellini, Maria Scupoli, Giuseppe Carli, Davide Facchinelli, Marco Cassatella, Patrizia Scapini and Cristina Tecchio _

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Oncotarget. 2016; 7:27676-27688. https://doi.org/10.18632/oncotarget.8507

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Abstract

Olivia Marini1,2, Cecilia Spina1, Elda Mimiola1, Adriana Cassaro1, Giovanni Malerba3, Giuseppe Todeschini1, Omar Perbellini1, Maria Scupoli1,4, Giuseppe Carli1, Davide Facchinelli1, Marco Cassatella2, Patrizia Scapini2, Cristina Tecchio1

1Department of Medicine, Section of Hematology and Bone Marrow Transplant Unit, University of Verona, Verona, Italy

2Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy

3Department of Neurological, Biomedical and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy

4Department of Inderdepartmental Laboratory for Medical Research (LURM), University of Verona, Verona, Italy

Correspondence to:

Cristina Tecchio, email: [email protected]

Keywords: granulocytic myeloid-derived suppressor cells, Hodgkin lymphoma, non-Hodgkin lymphoma, low-density neutrophils, normal-density neutrophils

Received: January 09, 2016     Accepted: March 18, 2016     Published: March 30, 2016

ABSTRACT

Human granulocytic myeloid-derived suppressor cells (G-MDSCs) have been described as low-density immunosuppressive CD66b+CD33dimHLA-DR-granulocytes that co-purify with mononuclear cells after density gradient centrifugation of blood from cancer patients. The role of G-MDSCs in Hodgkin (HL) and non-Hodgkin lymphoma (NHL) remains unclear.

The percentage and immunophenotype of CD66b+CD33dimHLA-DR-cells were analyzed in PBMCs from HL and B-cell NHL patients (n = 124) and healthy donors (n = 48). The immunosuppressive functions of these cells were tested in vitro. Correlations between CD66b+CD33dimHLA-DR-cells and patient clinicopathological features and outcome, were evaluated.

CD66b+CD33dimHLA-DR-cells were increased in PBMCs from HL and B-cell NHL patients as compared to healthy donors: 2.18 (0.02–70.92) vs 0.42 (0.04–2.97), p < 0.0001. Their percentage remained significantly higher even considering HL (n = 31), indolent (n = 31) and aggressive (n = 62) B-cell NHL patients separately: 1.54 (0.28–26.34), 2.15 (0.02–20.08), and 2.96 (0.25–70.92), respectively, p < 0.0001. CD66b+CD33dimHLA-DR-cells in patient PBMCs were mostly composed of mature CD11b+CD16+ low-density neutrophils in an activated status, as revealed by their higher CD11b and CD66b expression as compared to conventionally isolated (normal-density) autologous or healthy donor neutrophils. The in vitro depletion of CD66b+ cells from patient PBMCs restored the proliferation of autologous T cells. Higher frequencies of CD66b+CD33dimHLA-DR G-MDSCs correlated significantly with unfavorable prognostic index scores and a shorter freedom from disease progression.

PBMCs from HL and B-cell NHL patients contain a population of CD66b+CD33dimHLA-DR G-MDSCs, mostly composed of activated low-density neutrophils with immunosuppressive properties. These findings disclose a previously unknown G-MDSC-mediated mechanism of immune-escape in lymphomas, therefore anticipating possible targets for therapeutic interventions.


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