Breast cancer cell-derived microRNA-155 suppresses tumor progression via enhancing immune cell recruitment and anti-tumor function

Junfeng Wang; Quanyi Wang; Yinan Guan; Yulu Sun; Xiaozhi Wang; Kaylie Lively; Yuzhen Wang; Ming Luo; Julian A. Kim; E. Angela Murphy; Yongzhong Yao; Guoshuai Cai; Daping Fan

doi:10.1172/JCI157248

¹Department of Cell Biology and Anatomy, University of South Carolina, Columbia, United States of America

²Department of General Surgery, Nanjign University, Nanjing, China

³Department of Chemistry, Georgia State University, Atlanta, United States of America

⁴Department of Surgery, University of South Carolina, Columbia, United States of America

⁵Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, United States of America

⁶Department of Environmental Health Sciences, University of South Carolina, Columbia, United States of America

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¹Department of Cell Biology and Anatomy, University of South Carolina, Columbia, United States of America

²Department of General Surgery, Nanjign University, Nanjing, China

³Department of Chemistry, Georgia State University, Atlanta, United States of America

⁴Department of Surgery, University of South Carolina, Columbia, United States of America

⁵Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, United States of America

⁶Department of Environmental Health Sciences, University of South Carolina, Columbia, United States of America

Find articles by Wang, Q. in: JCI | PubMed | Google Scholar

¹Department of Cell Biology and Anatomy, University of South Carolina, Columbia, United States of America

²Department of General Surgery, Nanjign University, Nanjing, China

³Department of Chemistry, Georgia State University, Atlanta, United States of America

⁴Department of Surgery, University of South Carolina, Columbia, United States of America

⁵Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, United States of America

⁶Department of Environmental Health Sciences, University of South Carolina, Columbia, United States of America

Find articles by Guan, Y. in: JCI | PubMed | Google Scholar

¹Department of Cell Biology and Anatomy, University of South Carolina, Columbia, United States of America

²Department of General Surgery, Nanjign University, Nanjing, China

³Department of Chemistry, Georgia State University, Atlanta, United States of America

⁴Department of Surgery, University of South Carolina, Columbia, United States of America

⁵Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, United States of America

⁶Department of Environmental Health Sciences, University of South Carolina, Columbia, United States of America

Find articles by Sun, Y. in: JCI | PubMed | Google Scholar

¹Department of Cell Biology and Anatomy, University of South Carolina, Columbia, United States of America

²Department of General Surgery, Nanjign University, Nanjing, China

³Department of Chemistry, Georgia State University, Atlanta, United States of America

⁴Department of Surgery, University of South Carolina, Columbia, United States of America

⁵Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, United States of America

⁶Department of Environmental Health Sciences, University of South Carolina, Columbia, United States of America

Find articles by Wang, X. in: JCI | PubMed | Google Scholar

¹Department of Cell Biology and Anatomy, University of South Carolina, Columbia, United States of America

²Department of General Surgery, Nanjign University, Nanjing, China

³Department of Chemistry, Georgia State University, Atlanta, United States of America

⁴Department of Surgery, University of South Carolina, Columbia, United States of America

⁵Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, United States of America

⁶Department of Environmental Health Sciences, University of South Carolina, Columbia, United States of America

Find articles by Lively, K. in: JCI | PubMed | Google Scholar

¹Department of Cell Biology and Anatomy, University of South Carolina, Columbia, United States of America

²Department of General Surgery, Nanjign University, Nanjing, China

³Department of Chemistry, Georgia State University, Atlanta, United States of America

⁴Department of Surgery, University of South Carolina, Columbia, United States of America

⁵Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, United States of America

⁶Department of Environmental Health Sciences, University of South Carolina, Columbia, United States of America

Find articles by Wang, Y. in: JCI | PubMed | Google Scholar

¹Department of Cell Biology and Anatomy, University of South Carolina, Columbia, United States of America

²Department of General Surgery, Nanjign University, Nanjing, China

³Department of Chemistry, Georgia State University, Atlanta, United States of America

⁴Department of Surgery, University of South Carolina, Columbia, United States of America

⁵Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, United States of America

⁶Department of Environmental Health Sciences, University of South Carolina, Columbia, United States of America

Find articles by Luo, M. in: JCI | PubMed | Google Scholar |

¹Department of Cell Biology and Anatomy, University of South Carolina, Columbia, United States of America

²Department of General Surgery, Nanjign University, Nanjing, China

³Department of Chemistry, Georgia State University, Atlanta, United States of America

⁴Department of Surgery, University of South Carolina, Columbia, United States of America

⁵Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, United States of America

⁶Department of Environmental Health Sciences, University of South Carolina, Columbia, United States of America

Find articles by Kim, J. in: JCI | PubMed | Google Scholar

¹Department of Cell Biology and Anatomy, University of South Carolina, Columbia, United States of America

²Department of General Surgery, Nanjign University, Nanjing, China

³Department of Chemistry, Georgia State University, Atlanta, United States of America

⁴Department of Surgery, University of South Carolina, Columbia, United States of America

⁵Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, United States of America

⁶Department of Environmental Health Sciences, University of South Carolina, Columbia, United States of America

Find articles by Murphy, E. in: JCI | PubMed | Google Scholar

¹Department of Cell Biology and Anatomy, University of South Carolina, Columbia, United States of America

²Department of General Surgery, Nanjign University, Nanjing, China

³Department of Chemistry, Georgia State University, Atlanta, United States of America

⁴Department of Surgery, University of South Carolina, Columbia, United States of America

⁵Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, United States of America

⁶Department of Environmental Health Sciences, University of South Carolina, Columbia, United States of America

Find articles by Yao, Y. in: JCI | PubMed | Google Scholar |

¹Department of Cell Biology and Anatomy, University of South Carolina, Columbia, United States of America

²Department of General Surgery, Nanjign University, Nanjing, China

³Department of Chemistry, Georgia State University, Atlanta, United States of America

⁴Department of Surgery, University of South Carolina, Columbia, United States of America

⁵Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, United States of America

⁶Department of Environmental Health Sciences, University of South Carolina, Columbia, United States of America

Find articles by Cai, G. in: JCI | PubMed | Google Scholar

¹Department of Cell Biology and Anatomy, University of South Carolina, Columbia, United States of America

²Department of General Surgery, Nanjign University, Nanjing, China

³Department of Chemistry, Georgia State University, Atlanta, United States of America

⁴Department of Surgery, University of South Carolina, Columbia, United States of America

⁵Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, United States of America

⁶Department of Environmental Health Sciences, University of South Carolina, Columbia, United States of America

Find articles by Fan, D. in: JCI | PubMed | Google Scholar

J Clin Invest. https://doi.org/10.1172/JCI157248.
Copyright © 2022, Wang et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published August 4, 2022 - Version history

Evidence suggests that increased microRNA-155 (miR-155) expression in immune cells enhances anti-tumor immune responses. However, given the reported association of miR-155 to tumorigenesis in various cancers, a debate is provoked on whether miR-155 is oncogenic or tumor suppressive. We aimed to interrogate the impact of tumor miR-155 expression, particularly cancer cell-derived miR-155, on anti-tumor immunity in breast cancer. We performed bioinformatic analysis of human breast cancer databases, murine experiments, and human specimen examination. We revealed that higher tumor miR-155 levels correlate with a favorable anti-tumor immune profile and better patient outcomes. Murine experiments demonstrated that miR-155 overexpression in breast cancer cells enhanced T cell influx, delayed tumor growth, and sensitized the tumors to immune checkpoint blockade (ICB) therapy. Mechanistically, miR-155 overexpression in breast cancer cells upregulated their CXCL9/10/11 production, which was mediated by SOCS1 inhibition and increased pSTAT1/pSTAT3 ratio. We further found that serum miR-155 levels in breast cancer patients correlate with tumor miR-155 levels and tumor immune status. Our findings suggest that high serum and tumor miR-155 levels may be a favorable prognostic marker for breast cancer patients, and therapeutic elevation of miR-155 in breast tumors may improve the efficacy of ICB therapy via remodeling the anti-tumor immune landscape.

Version 1 (August 4, 2022): In-Press Preview

Breast cancer cell-derived microRNA-155 suppresses tumor progression via enhancing immune cell recruitment and anti-tumor function

Junfeng Wang,¹ Quanyi Wang,¹ Yinan Guan,² Yulu Sun,² Xiaozhi Wang,¹ Kaylie Lively,¹ Yuzhen Wang,¹ Ming Luo,³ Julian A. Kim,⁴ E. Angela Murphy,⁵ Yongzhong Yao,² Guoshuai Cai,⁶ and Daping Fan¹

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Breast cancer cell-derived microRNA-155 suppresses tumor progression via enhancing immune cell recruitment and anti-tumor function

Junfeng Wang,1 Quanyi Wang,1 Yinan Guan,2 Yulu Sun,2 Xiaozhi Wang,1 Kaylie Lively,1 Yuzhen Wang,1 Ming Luo,3 Julian A. Kim,4 E. Angela Murphy,5 Yongzhong Yao,2 Guoshuai Cai,6 and Daping Fan1

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Junfeng Wang,¹ Quanyi Wang,¹ Yinan Guan,² Yulu Sun,² Xiaozhi Wang,¹ Kaylie Lively,¹ Yuzhen Wang,¹ Ming Luo,³ Julian A. Kim,⁴ E. Angela Murphy,⁵ Yongzhong Yao,² Guoshuai Cai,⁶ and Daping Fan¹