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

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.