سلول های سرکوبگر مشتق از رده میلوئیدی بواسطه القای بیان ژن STAT3 باعث مهار سیستم ایمنی ضد توموری می شوند

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) سلول های سرکوبگر مشتق از رده میلوئیدی بواسطه القای بیان ژن STAT3 باعث مهار سیستم ایمنی ضد توموری می شوند. Journal of Cellular Physiology ــ 234 (4). pp. 3515-3525. شاپا 0021-9541

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Official URL: https://onlinelibrary.wiley.com/doi/10.1002/jcp.26...


Myeloid-Derived Suppressor Cells suppress antitumor immune Responses through STAT3 expression in patient 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 :شهریار هاشم زاده
نویسنده :Pascal H.G Duijf
نویسنده :بهزاد منصوری
نویسنده :وحید خاضع
نویسنده :علی محمدی
نویسنده :توحید کاظمی
نویسنده :مهدی یوسفی
نویسنده :میلاد اسدی
نویسنده :حامد محمدی
نویسنده :فرهاد بابایی
نویسنده مسئول :بهزاد برادران
Additional Information:Impact Factor (2018):4.522 Indexed in: ISI, Pubmed/Medline/Index Medicus, Scopus, 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
Faculty of Medicine > Department of Basic Sciences > Department of Microbiology
ID Code:11770
Deposited By: Dr elham safarzadeh
Deposited On:22 Feb 1398 11:02
Last Modified:30 Apr 1398 10:21

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