Oncotarget

Research Papers:

Myeloid-derived suppressor cell and macrophage exert distinct angiogenic and immunosuppressive effects in breast cancer

Zhaoxu Fang, Chengwen Wen, Xiaolan Chen, Rongping Yin, Chenglin Zhang, Xiaohua Wang and Yuhui Huang _

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Oncotarget. 2017; 8:54173-54186. https://doi.org/10.18632/oncotarget.17013

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Abstract

Zhaoxu Fang1,*, Chengwen Wen1,*, Xiaolan Chen2,*, Rongping Yin3, Chenglin Zhang3, Xiaohua Wang4 and Yuhui Huang1,5

1Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China

2Institute of Pediatric Research, Affiliated Children’s Hospital, Soochow University, Suzhou, China

3School of Nursing, Soochow University, Suzhou, China

4The First Affiliated Hospital of Soochow University/School of Nursing, Soochow University, Suzhou, China

5Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Soochow University, Suzhou, China

*These authors contributed equally to this work

Correspondence to:

Yuhui Huang, email: [email protected]

Xiaohua Wang, email: [email protected]

Keywords: myeloid-derived suppressor cell, tumor-associated macrophage, immunosuppression, angiogenesis, immunotherapy

Received: February 03, 2017     Accepted: March 30, 2017     Published: April 10, 2017

ABSTRACT

The immunosuppressive tumor microenvironment is a key obstacle to hinder a cancer immunotherapy. Myeloid-derived suppressor cells (MDSCs) have been considered as a major player in immunosuppression. In this study, we find that tumor-infiltrating MDSCs (tiMDSCs) are less immunosuppressive than tumor-associated macrophages (TAMs) in multiple murine orthotopic breast tumor models. Compared to TAMs, tiMDSCs produce higher levels of pro-inflammatory factors and lower levels of anti-inflammatory factors. Furthermore, tiMDSCs are preferentially located in hypoxic areas and are more pro-angiogenic than TAMs. Consistent with these functional disparities, a shift from tiMDSCs to TAMs is observed during the progression of breast cancer. Moreover, infiltration of tiMDSCs is also noted in distal colonization of breast cancer cells in the lung. Taken together, our findings indicate that tiMDSCs are more pro-angiogenic and promote tumor initiation, while TAMs are more immunosuppressive and facilitate tumor immune evasion. This study suggests that selectively targeting on TAMs could alleviate the immunosuppressive tumor microenvironment and potentiate cancer immunotherapy.


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