2. Academic Validation
  3. MARCO expression on myeloid-derived suppressor cells is essential for their differentiation and immunosuppression

MARCO expression on myeloid-derived suppressor cells is essential for their differentiation and immunosuppression

  • Cell Death Discov. 2025 Jul 22;11(1):337. doi: 10.1038/s41420-025-02627-1.
Sijia Liu # 1,  Binle Tian # 2 3,  Na Wang 4,  Zhilong Wang 5,  Wen Zhang 5,  Qi Li 6 7,  JianFei Wang 8 9,  Guo-Huang Fan 10,  Caicun Zhou 11 12
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
  • 2 Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Department of Antibody Development, Immunophage Biotech Co., Ltd, Shanghai, China.
  • 5 Department of Oncology, Immunophage Biotech Co., Ltd, Shanghai, China.
  • 6 Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. leeqi@sjtu.edu.cn.
  • 7 Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China. leeqi@sjtu.edu.cn.
  • 8 Executive Office, Immunophage Biotech Co., Ltd, Shanghai, China. jfwang@immunophage.com.cn.
  • 9 Shanghai Laboratory Animal Research Center, Shanghai, China. jfwang@immunophage.com.cn.
  • 10 Executive Office, Immunophage Biotech Co., Ltd, Shanghai, China. ghfan@immunophage.com.cn.
  • 11 Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. caicunzhoudr@163.com.
  • 12 Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. caicunzhoudr@163.com.
  • # Contributed equally.
PMID: 40695812 DOI: 10.1038/s41420-025-02627-1
Abstract

Myeloid-derived suppressor cells (MDSCs) significantly contribute to the immunosuppressive tumor microenvironment (TME), and targeted inhibition of MDSCs is a potential therapeutic strategy against Cancer. Here, we identify macrophage receptor with collagenous structure (MARCO) as a critical regulator of MDSC differentiation and immunosuppression in breast Cancer. The present study demonstrates that MARCO is expressed on MDSCs, and breast tumor-derived exosomes (TDEs) enriched with macrophage migration inhibitory factor (MIF) promote MDSC differentiation and amplify immunosuppressive activity by up-regulating MARCO. Genetic ablation of MARCO in a murine breast Cancer model attenuated tumor growth, accompanied by reduced monocytic MDSCs (M-MDSCs) and total tumor-associated macrophages (TAMs), along with enhanced infiltration of CD8+ T cells and natural killer (NK) cells. Furthermore, we developed a specific MARCO down-regulation-promoting monoclonal antibody that impeded TDE-induced MDSC differentiation and immunosuppression. In vivo, MARCO down-regulating antibody suppressed tumor growth and reprogrammed the TME by diminishing immunosuppressive MDSCs and TAMs and revitalizing CD8+ T cells and NK cells. Strikingly, combining the MARCO down-regulating antibody with PD-1 blockade synergistically enhanced anti-tumor efficacy. This work establishes MARCO as a key regulator of MDSC-mediated immunosuppression and presents a compelling case for the inclusion of MARCO as a therapeutic target in Cancer Immunotherapy.

Figures
Products
Inhibitors & Agonists
Other Products