title

اهمیت پروگنوستیک سلول های سرکوبگر مشتق از رده میلوئیدی در بیماران مبتلا به سرطان سینه

صفرزاده, الهام and هاشم زاده, شهریار and Duijf, Pascal H.G and منصوری, بهزاد and خاضع, وحید and محمدی, علی and کاظمی, توحید and یوسفی, مهدی and اسدی, میلاد and محمدی, حامد and بابایی, فرهاد and برادران, بهزاد (1397) اهمیت پروگنوستیک سلول های سرکوبگر مشتق از رده میلوئیدی در بیماران مبتلا به سرطان سینه. Journal of Cellular Physiology ــ 234 (4). pp. 3515-3525. شاپا 0021-9541

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Title

Circulatingmyeloid‐derived suppressor cells: An independent prognostic factor in patients with breast cancer

English 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.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :الهام صفرزاده
نویسنده مسئول :بهزاد برادران
Additional Information:IF: 3.923 Indexed in: ISI, Scopus, PubMed/ Medline, Embase
کلیدواژه ها (انگلیسی):breast cancer (BC), immunoediting, immunosuppressive, metastasis, myeloid‐derived suppressor , cells (MDSCs), tumor microenvironment
Subjects:QW Microbiology and Immunology
Divisions:Faculty of Medicine > Department of Basic Sciences > Department of Immunology
ID Code:11739
Deposited By: Dr elham safarzadeh
Deposited On:19 Mar 1398 14:54
Last Modified:19 Mar 1398 14:54

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