Nanodrug modified with engineered cancer cell membrane targets CDKs to activate PD-L1 antibody immunotherapy against liver metastasis of immune-desert colon cancer

First, CDK inhibitor (CDKi) delivered by nanodrug down-regulates phosphorylated retinoblastoma and phosphorylated RNA polymerase II and meanwhile arrests the G2/M cell cycle in CCLM to promote immunogenic signal release, stimulate dendritic cell maturation, and enhance CD8+ T cell infiltration. Moreover, CDKi suppresses the secretion of immunosuppressive cytokines in tumor-associated myeloid cells (TAMCs) sensitizing ICB therapy in CCLM of murine CT26 cell.

Notably, the great efficacy to activate immune responses is demonstrated in the patient-derived xenograft (PDX) model and the patient-derived organoid (PDO) model as well, revealing a clinical application potential. Overall, our study represents a promising therapeutic approach for targeting liver metastasis, remolding the TIME, and enhancing the response of MSS/pMMR CCLM to boost ICB immunotherapy.