Circulating myeloid‐derived suppressor cells: An independent prognostic factor in patients with breast cancer. Issue 4 (26th October 2018)

• Record Type: Journal Article
• Authors: Safarzadeh, Elham; Hashemzadeh, Shahryar; Duijf, Pascal H.G.; Mansoori, Behzad; Khaze, Vahid; Mohammadi, Ali; Kazemi, Tohid; Yousefi, Mehdi; Asadi, Milad; Mohammadi, Hamed; Babaie, Farhad; Baradaran, Behzad
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 4(2019:Apr.)
• Page Start: 3515
• Page End: 3525
• Publication Date: 2018-10-26
• Subjects: breast cancer (BC) -- immunoediting -- immunosuppressive -- metastasis -- myeloid‐derived suppressor cells (MDSCs) -- tumor microenvironment; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.26896
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Evading immune destruction is a hallmark of cancer. Myeloid‐derived suppressor cells (MDSCs), a heterogeneous population of myeloid immune cells, are thought to foster the establishment of an immunosuppressive tumor microenvironment, but it remains unclear how. This study aims to determine the levels of circulating MDSCs and their subpopulations and test their immunosuppressive functions in patients with breast cancer (BC). We analyzed the fractions of MDSCs in freshly isolated peripheral blood mononuclear cells of patients with BC and healthy donors using flow cytometry. Circulating MDSCs were further phenotyped using fluorescently labeled antihuman monoclonal antibodies. Coculture experiments revealed the effects of MDSCs on CD3 + T cell response. Moreover, we correlated circulating MDSC levels with clinicopathological features of patients with BC. We show that the fraction of HLA‐DR – CD33 + MDSCs in peripheral blood is about 10‐fold higher in patients with BC than in healthy control individuals. The levels of all MDSC subpopulations, including monocytic and granulocytic MDSCs, are significantly elevated. Coculture experiments of purified HLA‐DR – CD33 + MDSCs and CD3 + T cells demonstrate that T cell proliferation is more effectively inhibited by BC patient‐derived MDSCs than by healthy control MDSCs. Moreover, increased circulating MDSC levels robustly associate with advanced BC stage and positive lymph node status. By being more abundant and more effective T cell suppressors, BC patient‐derived circulating MDSCs exert a dual immunosuppressive effect. Our findings pave the way to develop novel diagnostic and immunotherapeutic strategies, aimed at detecting and inhibiting MDSCs in patients with BC. Abstract : Myeloid‐derived suppressor cells (MDSCs) are thought to foster the establishment of an immunosuppressive tumor microenvironment. By being more abundant and more effective T cell suppressors, breast cancer patient‐derived circulating MDSCs exert a dual immunosuppressive effect. Moreover, increased circulating MDSC levels robustly associate with advanced breast cancer stage and positive lymph node status.