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

Abstract

// Zhaoxu Fang 1, * , Chengwen Wen 1, * , Xiaolan Chen 2, * , Rongping Yin 3 , Chenglin Zhang 3 , Xiaohua Wang 4 and Yuhui Huang 1, 5 1 Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China 2 Institute of Pediatric Research, Affiliated Children’s Hospital, Soochow University, Suzhou, China 3 School of Nursing, Soochow University, Suzhou, China 4 The First Affiliated Hospital of Soochow University/School of Nursing, Soochow University, Suzhou, China 5 Key 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: hyhui20126@163.com Xiaohua Wang, email: sxwang2001@163.com 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.