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

被引:16
作者
Li, Jian [1 ]
Chen, Yuxiang [2 ]
Liao, Mingmei [3 ]
Yu, Shuyi [4 ]
Yuan, Binwen [1 ]
Jia, Zeming [1 ]
Zhou, Lin [1 ]
Tang, Yaping [1 ]
机构
[1] Cent South Univ, Xiangya Hosp, Dept Colorectal & Anal Surg, Gen Surg, Changsha 410008, Hunan, Peoples R China
[2] Cent South Univ, Xiangya Pharmaceut Coll, Changsha 410013, Hunan, Peoples R China
[3] Cent South Univ, Xiangya Hosp, Key Lab Nanobiol Technol, Natl Hlth Commiss, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China
[4] Cent South Univ, Adv Res Ctr, Changsha 410083, Hunan, Peoples R China
关键词
PD-L1; CTLA-4; siRNA; Colorectal cancer; Immune activation; IMMUNOTHERAPY; BLOCKADE;
D O I
10.1016/j.ygeno.2023.110646
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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-& gamma;, and TNF-& alpha; 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.
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页数:11
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