Exosomes-delivered PD-L1 siRNA and CTLA-4 siRNA protect against growth and tumor immune escape in colorectal cancer.

OBJECTIVE: This study aims to dissect impacts of exosomes-delivered PD-L1 and CTLA-4 siRNAs on colorectal cancer (CRC) progression and immune responses. METHODS: Exosomes containing PD-L1 siRNA and CTLA-4 siRNA were prepared and utilized to treat CRC cells to evaluate their effects. A tumor-bearing mouse model was established for verification. RESULTS: Exosomes containing PD-L1 siRNA and CTLA-4 siRNA repressed malignant features of CRC cells and restrained tumor growth and activated tumor immune responses in vivo. Co-culture of CRC cells treated with exosomes containing PD-L1 siRNA and CTLA-4 siRNA with human CD8+ T cells increased the percentage of CD8+ T cells, decreased the apoptotic rate of CD8+ T cells, elevated IL-2, IFN-γ, and TNF-α expression in cell supernatants, reduced adherent density of CRC cells, augmented the positive rate of CRC cells, and subdued tumor immune escape. CONCLUSION: Exosomes containing PD-L1 siRNA and CTLA-4 siRNA suppressed CRC progression and enhanced tumor immune responses.