Department of Colorectal and Anal Surgery, General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
Xiangya Pharmaceutical College, Central South University, Changsha, Hunan 410013, PR China.
Genomics. 2023 Jul;115(4):110646. doi: 10.1016/j.ygeno.2023.110646. Epub 2023 May 20.
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.
目的：本研究旨在剖析外泌体递送的 PD-L1 和 CTLA-4 siRNA 对结直肠癌（CRC）进展和免疫应答的影响。
方法：制备含有 PD-L1 siRNA 和 CTLA-4 siRNA 的外泌体，并用于处理 CRC 细胞以评估其作用。建立荷瘤小鼠模型进行验证。
结果：含有 PD-L1 siRNA 和 CTLA-4 siRNA 的外泌体抑制 CRC 细胞的恶性特征，抑制体内肿瘤生长并激活肿瘤免疫应答。用含有 PD-L1 siRNA 和 CTLA-4 siRNA 的外泌体处理的 CRC 细胞与人 CD8 T 细胞共培养，增加了 CD8 T 细胞的百分比，降低了 CD8 T 细胞的凋亡率，提高了细胞上清液中 IL-2、IFN-γ 和 TNF-α 的表达，降低了 CRC 细胞的黏附密度，增加了 CRC 细胞的阳性率，并抑制了肿瘤免疫逃逸。
结论：含有 PD-L1 siRNA 和 CTLA-4 siRNA 的外泌体抑制 CRC 进展并增强肿瘤免疫应答。
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