AG490逆轉(zhuǎn)膀胱癌細胞對樹突狀細胞的表型改變

2018年4月，首都醫(yī)科大學附屬北京世紀壇醫(yī)院臨床檢驗醫(yī)學科；泌尿細胞分子診斷北京市重點實驗室；北京大學第九臨床醫(yī)學院臨床檢驗醫(yī)學科（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老師研究團隊在《ONCOLOGY LETTERS》上發(fā)表論文：

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

“AG490逆轉(zhuǎn)膀胱癌細胞對樹突狀細胞的表型改變”

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：

過去的研究證實，腫瘤可以損害樹突狀細胞(dc)的功能，促進腫瘤逃逸。AG490是一種Janus激酶2/信號換能器和轉(zhuǎn)錄3激活因子抑制劑，已被證明可以誘導(dǎo)DCs成熟并抑制腫瘤細胞的生長。在本研究中，樹突狀細胞是由健康人外周血單個核細胞產(chǎn)生的。培養(yǎng)第5天，將dc與人膀胱癌pumc-91細胞共培養(yǎng)24 h，然后用磁珠純化。脂多糖誘導(dǎo)樹突狀細胞成熟。與pumc-91細胞共培養(yǎng)后，發(fā)現(xiàn)dc中人白細胞抗原-抗原D相關(guān)(HLA-DR)、分化簇(cd86)和CD80的表達減少，同時白細胞介素(IL)-10的產(chǎn)生增加，但IL-12p70的產(chǎn)生減少。此外，與pumc-91共培養(yǎng)的樹突狀細胞可抑制異體T細胞的增殖。最后，AG490恢復(fù)了HLA-DR、CD86和CD80的表達。這些數(shù)據(jù)表明，膀胱癌細胞可以抑制dc的抗原呈遞功能并誘導(dǎo)T細胞的能量。AG490可能部分逆轉(zhuǎn)膀胱癌細胞對dc的抑制作用，激活dc的免疫原性，誘導(dǎo)dc的抗腫瘤免疫應(yīng)答。

該論文中，人膀胱癌pumc-91的體外培養(yǎng)是使用Ausbian特級胎牛血清完成的。欲了解或購買Ausbian特級胎牛血清可以聯(lián)系北京締一生物400-166-8600.