Oncotarget

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Suppressive role of myeloid-derived suppressor cells (MDSCs) in the microenvironment of breast cancer and targeted immunotherapies

Dawei Shou, Liang Wen, Zhenya Song, Jian Yin, Qiming Sun and Weihua Gong _

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Oncotarget. 2016; 7:64505-64511. https://doi.org/10.18632/oncotarget.11352

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Abstract

Dawei Shou1,*, Liang Wen1,*, Zhenya Song2,*, Jian Yin3,*, Qiming Sun4 and Weihua Gong1

1 Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou City, People’s Republic of China

2 Department of Comprehensive Medicine, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou City, People’s Republic of China

3 Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, City Key Laboratory of Tianjin Cancer Center, Tianjin, People’s Republic of China

4 Department of Biochemistry, School of Medicine, Zhejiang University, Hangzhou City, People’s Republic of China

* These authors have contributed equally to this work

Correspondence to:

Weihua Gong, email:

Qiming Sun, email:

Keywords: myeloid-derived suppressor cells; breast cancer; microenvironment; immunotherapy

Received: March 02, 2016 Accepted: July 09, 2016 Published: August 17, 2016

Abstract

Myeloid-derived suppressor cells (MDSCs) play a pivotal role in promoting tumor growth and metastasis and can even decrease the efficacy of immunotherapy. In breast cancer, MDSCs are recruited mainly by breast cancer cells to form a tumor-favoring microenvironment to suppress the anti-tumor immune response. In addition, MDSCs can react directly with breast cancer cells. In this paper, we describe several ways to recruit MDSCs in breast cancer, including breast cancer cell-derived cytokines and chemokines. The intracellular pathways in MDSCs during recruitment are classified as the STAT3-NF-κB-IDO pathway, the STAT3/IRF-8 pathway and the PTEN/Akt pathway. MDSCs act on T cells and NK cells to suppress the body’s immunity, and via IL-6 trans-signaling, promote breast cancer directly. We further describe MDSC-targeted immune therapies for breast cancer, which are classified as: preventing the formation of MDSCs, eliminating MDSDCs, and reducing the products of MDSCs. Furthermore, MDSC-targeted immunotherapy potentiates the effect of the other immunotherapies. Based on the facts that MSDCs have significant roles in breast cancer malignant behaviors and can be suppressed by various strategies, we do believe MDSC-targeted immunotherapy presents a broad prospect in the future.


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