2018年4月发表论文：AG490逆转膀胱癌细胞对树突状细胞的表型改变

摘要：2018年4月，首都医科大学附属北京世纪坛医院临床检验医学科；泌尿细胞分子诊断北京市重点实验室；北京大学第九临床医学院临床检验医学科（Department of Clinical Laboratory Medicine, Beijing Shijitan Ho

2018年4月，首都医科大学附属北京世纪坛医院临床检验医学科；泌尿细胞分子诊断北京市重点实验室；北京大学第九临床医学院临床检验医学科（Department of Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University；Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics；Department of Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing 100038, P.R. China) WEIGANG XIU老师研究团队在《ONCOLOGY LETTERS》上发表论文：

“AG490 reverses phenotypic alteration of dendritic cells by bladder cancer cells”

“AG490逆转膀胱癌细胞对树突状细胞的表型改变”

Abstract

Past studies have confirmed that tumors can impair the function of dendritic cells (DCs) and promote tumor evasion. AG490, a Janus kinase 2/signal transducer and activator of transcription 3 inhibitor, has been shown to induce maturation of DCs and inhibit the growth of tumor cells. In the present study, DCs were generated from healthy human peripheral blood mononuclear cells. On day 5 of culture, the DCs were co-cultured with human bladder cancer pumc-91 cells for 24 h, and then purified using magnetic beads. The maturation of the DCs was induced by lipopolysaccharide. Subsequent to co-culture with pumc-91 cells, the expression of human leukocyte antigen-antigen D related (HLA-DR), cluster of differentiation (CD)86 and CD80 was found to be reduced in the DCs, accompanied by increased production of interleukin (IL)-10, but decreased production of IL-12p70. Furthermore, the DCs co-cultured with pumc-91 inhibited the proliferation of allogeneic T cells. Finally, AG490 restored the expression of HLA-DR, CD86 and CD80. These data identified that bladder cancer cells could inhibit the antigen-presenting function of the DCs and induce anergy in T cells. AG490 may partly reverse this inhibitory effect of bladder cancer cells on DCs, activate immunogenicity and induce the antitumor immunity response of DCs.

摘要

过去的研究证实，肿瘤可以损害树突状细胞(dc)的功能，促进肿瘤逃逸。AG490是一种Janus激酶2/信号换能器和转录3激活因子抑制剂，已被证明可以诱导DCs成熟并抑制肿瘤细胞的生长。在本研究中，树突状细胞是由健康人外周血单个核细胞产生的。培养第5天，将dc与人膀胱癌pumc-91细胞共培养24 h，然后用磁珠纯化。脂多糖诱导树突状细胞成熟。与pumc-91细胞共培养后，发现dc中人白细胞抗原-抗原D相关(HLA-DR)、分化簇(cd86)和CD80的表达减少，同时白细胞介素(IL)-10的产生增加，但IL-12p70的产生减少。此外，与pumc-91共培养的树突状细胞可抑制异体T细胞的增殖。最后，AG490恢复了HLA-DR、CD86和CD80的表达。这些数据表明，膀胱癌细胞可以抑制dc的抗原呈递功能并诱导T细胞的能量。AG490可能部分逆转膀胱癌细胞对dc的抑制作用，激活dc的免疫原性，诱导dc的抗肿瘤免疫应答。

该论文中，人膀胱癌pumc-91的体外培养是使用Ausbian特级胎牛血清完成的。