Dendritic cell-liposome conjugates reverse immunosuppressive tumor microenvironment for inhibiting colitis-associated colorectal cancer

  • Acta Pharmacol Sin. 2025 Aug 8. doi: 10.1038/s41401-025-01614-7.
Wen-Zhe Yi  #  1  2 ,  Xin-di Qian  #  1  3 ,  Xiao-Xuan Xu  1  2 ,  Rong Pu  4 ,  Dan Yan  1 ,  Zhi-Wen Zhao  1  2 ,  Ya-Ping Li  5  6  7  8 ,  Dang-Ge Wang  9
Affiliations
  • 1. State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 2. University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3. Department of Medical Ultrasound and Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People's Hospital, Ultrasound Research and Education Institute, School of Medicine Tongji University, Shanghai, 200072, China.
  • 4. Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 5. State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. [email protected].
  • 6. University of Chinese Academy of Sciences, Beijing, 100049, China. [email protected].
  • 7. Nanjing University of Chinese Medicine, Nanjing, 210023, China. [email protected].
  • 8. Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, 264000, China. [email protected].
  • 9. Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China. [email protected].
  • # Contributed equally.
PMID: 40781495 DOI: 10.1038/s41401-025-01614-7
Abstract

The progression of colitis-associated Cancer (CAC) is strongly associated with bone marrow-derived immunosuppressive cells (MDSCs). Although CAC could be suppressed by inducing MDSCs Apoptosis, the immunosuppressive tumor microenvironment (TME) maintains immune homeostasis by upregulating M2-type tumor-associated macrophages (TAMs), thus leading to adaptive immune tolerance. Herein, we develop a dendritic cell (DC)-liposome conjugate to reverse immunosuppressive TME, showing remarkable efficiency against colorectal Cancer. The DC-liposome conjugate is fabricated by conjugating resolvin E1-loaded liposomes with Fas ligand-transfected DCs, which eliminates tumor-infiltrated Fas+ MDSCs and enhances TAM phagocytosis in tumors. It shows significant therapeutic effects in preclinical CAC models and alleviates severe colitis when combined with immune checkpoint inhibitors. This study provides a feasible and customized cell-drug conjugate to overcome immunosuppressive TME for enhancing CAC immunotherapy.

Keywords
colitis-associated cancer; dendritic cell; liposome; marrow-derived immunosuppressive cell; tumor-associated macrophage.
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