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阴性免疫因子可能在宫颈癌局部肿瘤免疫状态中占主导地位并促进肿瘤发生。

Negative immune factors might predominate local tumor immune status and promote carcinogenesis in cervical carcinoma.

作者信息

Zhao Minyi, Li Yang, Wei Xing, Zhang Qian, Jia Hongran, Quan Shimin, Cao Di, Wang Li, Yang Ting, Zhao Juan, Pei Meili, Tian Sijuan, Yu Yang, Guo Yanping, Yang Xiaofeng

机构信息

Department of Obstetrics and Gynecology, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, China.

Department of Obstetrics and Gynecology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

Virol J. 2017 Jan 13;14(1):5. doi: 10.1186/s12985-016-0670-8.

Abstract

BACKGROUND

The disequilibrium of local immune microenvironment is an essential element during tumorigenesis.

METHOD

By conducting real-time polymerase chain reaction, we identified the mRNA level of immune factors, FoxP3 (forkhead box protein P3), CCL22/CCR4 (chemokine (C-C motif) ligand 22/CC chemokine receptor 4), OX40L/OX40 (tumor necrosis factor superfamily member 4/tumor necrosis factor receptor superfamily member 4) and Smad3 (SMAD family member 3) in neoplastic foci and its periphery tissues from 30 cases of squamous cervical carcinoma and 20 cases of normal cervix.

RESULT

The FoxP3, CCL22 and CCR4 mRNA level in local immune microenvironment of normal cervix was lower than that in cervical cancer. While OX40L, OX40 and Smad3 mRNA level profile in normal cervix was higher than that in cervical cancer. Beyond individual effect, the pairwise positive correlations were demonstrated among the mRNA level of FoxP3, CCL22 and CCR4. The mRNA level of OX40 negatively correlated with CCL22, but positively correlated with Smad3. Moreover, the mRNA level of FoxP3 and CCL22 was increased while Smad3 was decreased in cervical tissue with HPV (human papilloma virus) infection.

CONCLUSION

Our data yields insight into the roles of these immune factors in cervical carcinogenesis. It may therefore be that, in microenvironment of cervical squamous cell carcinoma, along with the context of HPV infection, negative immune regulators FoxP3, CCL22 and CCR4 might overwhelm positive immune factors OX40L, OX40 and Smad3, giving rise to an immunosuppressive status and promote the progression of cervical carcinogenesis.

TRIAL REGISTRATION

Not applicable.

摘要

背景

局部免疫微环境失衡是肿瘤发生过程中的一个关键因素。

方法

通过实时聚合酶链反应,我们检测了30例宫颈鳞癌和20例正常宫颈的肿瘤病灶及其周边组织中免疫因子FoxP3(叉头框蛋白P3)、CCL22/CCR4(趋化因子(C-C基序)配体22/C-C趋化因子受体4)、OX40L/OX40(肿瘤坏死因子超家族成员4/肿瘤坏死因子受体超家族成员4)和Smad3(SMAD家族成员3)的mRNA水平。

结果

正常宫颈局部免疫微环境中FoxP3、CCL22和CCR4的mRNA水平低于宫颈癌。而正常宫颈中OX40L、OX40和Smad3的mRNA水平高于宫颈癌。除个体效应外,FoxP3、CCL22和CCR4的mRNA水平之间存在两两正相关。OX40的mRNA水平与CCL22呈负相关,但与Smad3呈正相关。此外,HPV(人乳头瘤病毒)感染的宫颈组织中FoxP3和CCL22的mRNA水平升高,而Smad3的mRNA水平降低。

结论

我们的数据揭示了这些免疫因子在宫颈癌发生中的作用。因此,在宫颈鳞状细胞癌的微环境中,在HPV感染的背景下,负性免疫调节因子FoxP3、CCL22和CCR4可能会压倒正性免疫因子OX40L、OX40和Smad3,导致免疫抑制状态并促进宫颈癌的进展。

试验注册

不适用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a41d/5237320/e29b1aba5b9d/12985_2016_670_Fig1_HTML.jpg

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