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4-1BB 抗体通过 NKG2D 激动剂与 IL-27 的联合增强自然杀伤细胞对前列腺癌细胞的细胞毒性活性。

4-1BB antibody enhances cytotoxic activity of natural killer cells against prostate cancer cells via NKG2D agonist combined with IL-27.

机构信息

Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

出版信息

Immunotherapy. 2022 Sep;14(13):1043-1053. doi: 10.2217/imt-2021-0232. Epub 2022 Jul 19.

Abstract

To enhance the cytotoxicity of natural killer (NK) cells against prostate cancer cells via NKG2D agonist, with 4-1BB antibody and IL-27 combination. FACS was used to detect degranulation and cell surface receptors in NK cells isolated from healthy donors. Cytokine concentrations were measured using ELISA. NK-cell cytotoxicity was analyzed using Cell Counting Kit-8. NKG2D agonist, 4-1BB antibody and IL-27 combination treatment improved the activating receptor expression and IFN-γ and TNF-α secretion but decreased the suppressive receptor CD158a expression and IL-10 secretion in NK cells. The combined treatment enhanced NK-cell cytotoxicity against both PC3 and DU145 cells with concurrent enhanced STAT3 activation. 4-1BB antibody and IL-27 improved NKG2D agonist function in NK cells against prostate cancer cells.

摘要

通过 NKG2D 激动剂、4-1BB 抗体和 IL-27 的联合作用,增强自然杀伤 (NK) 细胞对前列腺癌细胞的细胞毒性。使用 FACS 检测从健康供体中分离的 NK 细胞的脱颗粒和细胞表面受体。使用 ELISA 测量细胞因子浓度。使用 Cell Counting Kit-8 分析 NK 细胞的细胞毒性。NKG2D 激动剂、4-1BB 抗体和 IL-27 的联合治疗可改善 NK 细胞的激活受体表达和 IFN-γ 和 TNF-α 分泌,但降低抑制性受体 CD158a 表达和 IL-10 分泌。联合治疗增强了 NK 细胞对 PC3 和 DU145 细胞的细胞毒性,同时增强了 STAT3 的激活。4-1BB 抗体和 IL-27 提高了 NK 细胞针对前列腺癌细胞的 NKG2D 激动剂功能。

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