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源自宫颈癌的间充质基质细胞会产生大量腺苷以抑制细胞毒性T淋巴细胞功能。

Mesenchymal stromal cells derived from cervical cancer produce high amounts of adenosine to suppress cytotoxic T lymphocyte functions.

作者信息

de Lourdes Mora-García María, García-Rocha Rosario, Morales-Ramírez Omar, Montesinos Juan José, Weiss-Steider Benny, Hernández-Montes Jorge, Ávila-Ibarra Luis Roberto, Don-López Christian Azucena, Velasco-Velázquez Marco Antonio, Gutiérrez-Serrano Vianey, Monroy-García Alberto

机构信息

Immunobiology Laboratory, Cellular Differentiation and Cancer Unit, FES-Zaragoza, UNAM, Mexico City, Mexico.

Immunology and Cancer Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City, Mexico.

出版信息

J Transl Med. 2016 Oct 26;14(1):302. doi: 10.1186/s12967-016-1057-8.

DOI:10.1186/s12967-016-1057-8
PMID:27782859
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5080842/
Abstract

BACKGROUND

In recent years, immunomodulatory mechanisms of mesenchymal stem/stromal cells (MSCs) from bone marrow and other "classic" sources have been described. However, the phenotypic and functional properties of tumor MSCs are poorly understood. The aim of this study was to analyze the immunosuppressive capacity of cervical cancer-derived MSCs (CeCa-MSCs) on effector T lymphocytes through the purinergic pathway.

METHODS

We determined the expression and functional activity of the membrane-associated ectonucleotidases CD39 and CD73 on CeCa-MSCs and normal cervical tissue-derived MSCs (NCx-MSCs). We also analyzed their immunosuppressive capacity to decrease proliferation, activation and effector cytotoxic T (CD8+) lymphocyte function through the generation of adenosine (Ado).

RESULTS

We detected that CeCa-MSCs express higher levels of CD39 and CD73 ectonucleotidases in cell membranes compared to NCx-MSCs, and that this feature was associated with the ability to strongly suppress the proliferation, activation and effector functions of cytotoxic T-cells through the generation of large amounts of Ado from the hydrolysis of ATP, ADP and AMP nucleotides.

CONCLUSIONS

This study suggests that CeCa-MSCs play an important role in the suppression of the anti-tumor immune response in CeCa through the purinergic pathway.

摘要

背景

近年来,已对来自骨髓和其他“经典”来源的间充质干/基质细胞(MSC)的免疫调节机制进行了描述。然而,肿瘤来源的MSC的表型和功能特性仍知之甚少。本研究旨在通过嘌呤能途径分析宫颈癌来源的MSC(CeCa-MSC)对效应T淋巴细胞的免疫抑制能力。

方法

我们测定了CeCa-MSC和正常宫颈组织来源的MSC(NCx-MSC)上膜相关外切核苷酸酶CD39和CD73的表达及功能活性。我们还分析了它们通过生成腺苷(Ado)来降低增殖、激活及效应细胞毒性T(CD8+)淋巴细胞功能的免疫抑制能力。

结果

我们检测到,与NCx-MSC相比,CeCa-MSC在细胞膜上表达更高水平的CD39和CD73外切核苷酸酶,并且这一特征与通过将ATP、ADP和AMP核苷酸水解生成大量Ado来强烈抑制细胞毒性T细胞的增殖、激活及效应功能的能力相关。

结论

本研究表明,CeCa-MSC通过嘌呤能途径在宫颈癌的抗肿瘤免疫反应抑制中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/318b23ccda23/12967_2016_1057_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/38d63c48103e/12967_2016_1057_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/c80137a8d691/12967_2016_1057_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/35a4831e72e0/12967_2016_1057_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/ecdbf7e1f595/12967_2016_1057_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/ae4f8be85299/12967_2016_1057_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/e6b42e01f929/12967_2016_1057_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/318b23ccda23/12967_2016_1057_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/38d63c48103e/12967_2016_1057_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/c80137a8d691/12967_2016_1057_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/35a4831e72e0/12967_2016_1057_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/ecdbf7e1f595/12967_2016_1057_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/ae4f8be85299/12967_2016_1057_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/e6b42e01f929/12967_2016_1057_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb3/5080842/318b23ccda23/12967_2016_1057_Fig7_HTML.jpg

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