RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Roles of immune cells in the concurrence of Echinococcus granulosus sensu lato infection and hepatocellular carcinoma.
Roles of immune cells in the concurrence of Echinococcus granulosus sensu lato infection and hepatocellular carcinoma.
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免疫细胞在抗寄生虫感染和恶性肿瘤免疫应答中均发挥关键作用。大量证据提示,细粒棘球绦虫广义复合群(E. granulosus s.l.)感染与肝细胞癌(HCC)发生可能存在关联。
本研究旨在观察免疫细胞在皮下病灶形成中的关键作用;研究将HepG2细胞单独或与E. granulosus s.l.原头蚴(PSC)共同移植。对照组将HepG2细胞皮下注射至裸鼠;共移植组将HepG2细胞与高剂量PSC混合后皮下注射。自移植第25天起每4天测量皮下病灶体积,第37天切除病灶进一步研究,观察基本病理及功能变化,并通过免疫组化和qRT-PCR检测Ki67、Bcl-2、Caspase3、α-SMA、T细胞标志物(CD3、CD4、CD8)、PD1/PD-L1及NK细胞标志物(CD16、CD56)。皮下病灶体积逐渐增大,出现病理异质性肿瘤细胞,共移植组表现更明显。与对照组相比,共移植组增殖标志物Ki67和Bcl-2表达较高;凋亡标志物Caspase3则在对照组中检测水平较高,提示PSC可能促进HCC发生发展。有趣的是,共移植组皮下病灶合成和储存糖原的功能更强。共移植组胶原及α-SMA阳性细胞也多于对照组。最重要的是,HepG2与PSC共同移植后,T细胞标志物、PD1/PD-L1及NK细胞标志物表达均显著增加。E. granulosus s.l.可能促进HCC发展,且与T细胞和NK细胞免疫应答密切相关。
Immune cells are pivotal players in the immune responses against both parasitic infection and malignancies. Substantial evidence demonstrated that there may exist possible relationship between echinococcus granulus sensu lato (E. granulosus s. l.) infection and hepatocellular carcinoma (HCC) development.
Thus, this study aimed to observe crucial roles of immune cells in the formation of subcutaneous lesions after transplanting HepG2 cell lines with or without E. granulosus s. l. protoscoleces (PSCs). HepG2 cell lines were subcutaneously injected into nude mice in the control group.
In the co-transplantation group, HepG2 cells were subcutaneously co-injected with high dosage of E. granulosus s. l. PSCs. From the 25th day of transplantation, volume of subcutaneous lesions was measured every four days, which were removed at the 37th day for further studies. Basic pathological and functional changes were observed.
Moreover, expression of Ki67, Bcl-2, Caspase3, -smooth muscle actin ( -SMA), T cell markers (CD3, CD4, CD8), PD1/PD-L1, nature killer (NK) cell markers (CD16, CD56) were further detected by immunohistochemical staining and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Subcutaneous lesions were gradually increased in volume and there occurred pathologically heterogeneous tumor cells, which were more significant in the co-transplantation group. Compared to the control group, expression of proliferation markers Ki67 and Bcl-2 was at higher levels in the co-transplantation group. Reversely, apoptotic marker Caspase3 was highly detected in the control group, suggesting promoting effects of E.
granulosus s. l. PSCs on HCC development. Interestingly, subcutaneous lesions of the co-transplantation group were more functional in synthesizing and storing glycogen. Collagen and -SMA + cells were also at higher levels in the co-transplantation group than those in the control group.
Most importantly, co-transplantation of HepG2 cells with E. granulosus s. l. PSCs led to significant increase in the expression of T cell markers, PD1/PD-L1 and NK cells markers. E. granulosus s. l. may have promoting effects on HCC development, which was closely associated with the immune responses of T cells and NK cells.
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