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

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+CD33dim HLA-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.