Dendritic cell-liposome conjugates reverse immunosuppressive tumor microenvironment for inhibiting colitis-associated colorectal cancer
Wen-zhe Yi1,2,
Xin-di Qian1,3,
Xiao-xuan Xu1,2,
Rong Pu4,
Dan Yan1,
Zhi-wen Zhao1,2,
Ya-ping Li1,2,4,5,
Dang-ge Wang6
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 Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264000, China
6 Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
Correspondence to: Ya-ping Li: ypli@simm.ac.cn, Dang-ge Wang: dg_wang@sjtu.edu.cn,
DOI: 10.1038/s41401-025-01614-7
Received: 7 February 2025
Accepted: 11 June 2025
Advance online: 8 August 2025
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.
