Abstract 5328: Expansion of CD11b+CD33lowCD15high immunosuppressive myeloid cell population in patients with bladder carcinoma

Abstract

Abstract Recent studies highlighted the immunoregulatory role of CD11b myeloid cells in cancer-associated immune non-responsiveness. Increased presence of myeloid-derived suppressor cells (MDSC) is one of the major factors responsible for immune suppression in tumor hosts. Here we describe the expanded CD11b myeloid cell subset in peripheral blood obtained from patients with bladder cancer. Based on expression of CD33 and CD15 myeloid cells markers, the circulating CD11b-positive cells in patients with bladder cancer could be subdivided into two major subpopulations: CD33lowCD15high and CD33highCD15low. First subpopulation (CD11b+CD33lowCD15high cells) has granulocyte-type morphology, express G-CSF receptor (CD114) and secrete elevated amounts of pro-inflammatory cytokines and chemokines such as G-CSF, MCP-1 MIP-1alpha, MIP-1beta. Second major myeloid cell subset from cancer patients (CD11b+CD33high CD15lowcells) displays a monocyte-type cell morphology and co-express CD14, M-CSF receptor (CD115), CCR2 and HLA-DR. We show here that proportion of granulocytic CD33lowCD15high cells is highly elevated in cancer patients as compared to healthy individuals. Patients with bladder cancer but not healthy volunteers show weak T cell proliferative response after in vitro stimulation. We demonstrate that granulocyte-type CD33lowCD15high cell population is involved in T cell hyporesponsiveness, since specific depletion of this cell subset restored the T cell proliferation. Obtained results suggest that fraction of PBMC in patients with bladder cancer patients contains markedly elevated proportion of CD11b+CD33lowCD15high granulocyte-type myeloid cell population which contributes to cancer-associated inflammation and tumor-induced immune suppression. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5328.