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首页> 外文期刊>International Journal of Clinical and Experimental Pathology >Combined induction with anti-PD-1 and anti-CTLA-4antibodies provides synergistic antitumor effectsin DC-CIK cells in renal carcinoma cell lines
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Combined induction with anti-PD-1 and anti-CTLA-4antibodies provides synergistic antitumor effectsin DC-CIK cells in renal carcinoma cell lines

机译：与抗PD-1和抗CTLA-4抗体联合诱导可在肾癌细胞系的DC-CIK细胞中发挥协同抗肿瘤作用

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Immune escape of cancer cells has become the main challenge in the immunocytotherapy field. In thisstudy, we analyzed the cytotoxicity of DC-CIK cells induced by anti-PD-1 and anti-CTLA-4 antibodies in RCC cell lines.Flow cytometry analysis was performed to analyze the immune phenotypes of DC-CIK cells. Click-iT EdU assay wasperformed to analyze the proliferation of DC-CIK cells. ELISA analysis was performed to detect the expression ofcytokines in DC-CIK cells. Compared with DC-CIK cells without any treatment, the growth inhibition rate was significantlyhigher in the other three groups. Moreover, combined induction with anti-PD-1 plus anti-CTLA-4 antibodiesprovides synergistic antitumor effects of DC-CIK cells in renal carcinoma cell lines. The combined treatment promotedDC-CIK cell proliferation and differentiation into CD3+CD56+ NKT cells and CD3+CD8+ CTL cells. Compared withthe control group, combined treatment significantly up-regulated the secretion of immune-stimulatory cytokines,such as IFN-γ and TNF-α, and down-regulated the secretion of the immunosuppressive cytokine IL-10. Furthermore,the co-induction promoted the early activation of DC-CIK cells. These results indicated the co-induction with antiPD-1plus anti-CTLA-4 antibodies improved antitumor effects of DC-CIK cells by promoting proliferation, differentiation,and early activation and regulating the secretion of immune-stimulatory and suppressive cytokines in renalcarcinoma cell lines.
机译：癌细胞的免疫逃逸已成为免疫细胞治疗领域的主要挑战。本研究分析了抗PD-1和抗CTLA-4抗体诱导的DC-CIK细胞在RCC细胞系中的细胞毒性。进行流式细胞术分析DC-CIK细胞的免疫表型。进行Click-iT EdU分析以分析DC-CIK细胞的增殖。进行ELISA分析以检测DC-CIK细胞中细胞因子的表达。与未经任何处理的DC-CIK细胞相比，其他三组的生长抑制率均明显更高。此外，与抗PD-1加抗CTLA-4抗体的联合诱导在肾癌细胞系中提供了DC-CIK细胞的协同抗肿瘤作用。联合处理促进DC-CIK细胞增殖和分化成CD3 + CD56 + NKT细胞和CD3 + CD8 + CTL细胞。与对照组相比，联合治疗显着上调了免疫刺激细胞因子如IFN-γ和TNF-α的分泌，并下调了免疫抑制细胞因子IL-10的分泌。此外，共诱导促进了DC-CIK细胞的早期活化。这些结果表明与抗PD-1plus抗CTLA-4抗体的共诱导通过促进肾癌细胞系中的增殖，分化和早期活化以及调节免疫刺激性和抑制性细胞因子的分泌来改善DC-CIK细胞的抗肿瘤作用。

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