Experimental immunotherapy study on colon cancer by lgr5 activated dendritic cells to induce antigen-specific CD8+ cytotoxic T lymphocytes

doi:10.16098/j.issn.0529-1356.2017.04.010

Abstract

Abstract:

Objective To observe the immunotherapy effect on colon cancer by leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) activated by dexxeperimental basis for colon cancer immunotherapy. Methods After dendritic cells (DCs) maturation induced by Lgr5, surface molecules, interleukin (IL)-12, and IL-10 of DCs were detected. Subsequently, Lgr5 antigen specific CD8⁺ cytotoxic T lymphocyte (CTL) was induced by Lgr5-DC. The killing effect and interferon (IFN)-γ of Lgr5-DC-CD8⁺ CTL on normal colonic epithelial cells CCD-18Co and colon cancer cell HT29 were tested. After Lgr5-DC-CD8+ CTL treatment, tumor volume in BALB/C-nu/nu mice was detected. The morphology of tumor tissue after treatment was observed by tissue staining. Results Compared with PBS, Lgr5 protein stimulation significantly increased surface markers DC80, DC83, DC86 and HLA-DR levels, and up to 3.29, 3.06, 2.90 and 6.93 times (P＜0.05)respectively. Lgr5 stimulation significantly stimulated the release of IL-12 and significantly reduced the secretion of IL-10 (P＜0.05). DC-CD8⁺ CTL and Lgr5-DC-CD8⁺CTL. Both resulted in a small amount of CCD-18Co cell killing (P＞0.05), but the killing rate of Lgr5-DC-CD8⁺ CTL on HT29 cells was 4.40 times as much as that of DC-CD8⁺ CTL. Tissue staining showed that Lgr5-DC-CD8⁺ CTL treatment resulted in significant pathological changes and BAX expression in tumor tissues. Conclusion Lgr5 protein stimulated the maturation of DCs cells that induced the production of Lgr5 antigen specific CD8⁺ CTL. Lgr5-DC-CD8⁺ CTL can effectively kill tumor cells and delay the growth of tumor.

Key words:

Leucine-rich repeat-containing G-protein collpled receptor 5, Dendritic cell, Cytotoxic T lymphocyte, Colon cancer, Immunotherapy, Mouse

MA Gang YANG Qing-qiang HE Xing-zhuang. Experimental immunotherapy study on colon cancer by lgr5 activated dendritic cells to induce antigen-specific CD8+ cytotoxic T lymphocytes[J]. Acta Anatomica Sinica, 2017, 48(4): 428-433.

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