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

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.