Tumor-induced myeloid-derived suppressor cells promote tumor progression through oxidative metabolism in human colorectal cancer.
Tumor-induced myeloid-derived suppressor cells promote tumor progression through oxidative metabolism in human colorectal cancer.
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肿瘤诱导的骨髓源性抑制细胞通过人结直肠癌的氧化代谢促进肿瘤进展
DOI：
10.1186/s12967-015-0410-7
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发表时间：
2015-02-01
影响因子：
7.4
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
OuYang LY;Wu XJ;Ye SB;Zhang RX;Li ZL;Liao W;Pan ZZ;Zheng LM;Zhang XS;Wang Z;Li Q;Ma G;Li J
背景骨髓源性抑制细胞（MDSC）的扩增已在包括结直肠癌（CRC）在内的人类实体瘤中得到证实。然而，这些肿瘤相关的MDSCs的性质和它们与CRC中的肿瘤细胞的相互作用仍然知之甚少。MethodsThe百分比和表型的MDSCs在外周血和肿瘤和癌旁组织从CRC患者，以及这些MDSCs的临床相关性，进行了评估。纳入匹配的健康供体作为对照。在体外共培养系统中研究了MDSCs与T细胞或肿瘤细胞的相互作用，并对MDSCs对T细胞或肿瘤细胞作用的分子机制进行了评价。结果发现CRC患者原发肿瘤组织和外周血中CD33 + CD11b + HLA-DR − MDSCs水平升高，且循环中MDSCs水平升高与晚期TNM分期和淋巴结转移相关。结直肠癌根治性切除术可显著降低循环中MDSC和CD4 + CD25highFOXP3+调节性T细胞的比例。此外，这些肿瘤诱导的MDSC可以通过细胞与细胞接触抑制T细胞增殖并促进CRC细胞生长。这种影响可以被废除的氧化代谢的抑制，包括生产一氧化氮（NO），和活性氧（ROS）。结论我们的研究结果揭示了MDSCs，T细胞和癌细胞在CRC发病机制之间的功能相互依赖性。了解MDSC对T细胞和肿瘤细胞的影响将有助于在CRC患者中建立免疫策略。
BackgroundExpansions of myeloid-derived suppressor cells (MDSCs) have been identified in human solid tumors, including colorectal cancer (CRC). However, the nature of these tumor-associated MDSCs and their interactions with tumor cells in CRC are still poorly understood.MethodsThe percentages and phenotype of MDSCs in peripheral blood and tumorous and paraneoplastic tissues from CRC patients, as well as the clinical relevance of these MDSCs, were assessed. Age-matched healthy donors were included as controls. The interaction between MDSCs and T cells or tumor cells was investigated in a coculture systemin vitro, and the molecular mechanism of the effect of MDSCs on T cells or tumor cells was evaluated.ResultsWe discovered that CRC patients had elevated levels of CD33+CD11b+HLA-DR−MDSCs in primary tumor tissues and in peripheral blood, and the elevated circulating MDSCs were correlated with advanced TNM stages and lymph node metastases. Radical resection significantly decreases the proportions of circulating MDSCs and CD4+CD25highFOXP3+regulatory T cells.In vitro, CRC cells mediate the promotion of MDSC induction. Moreover, these tumor-induced MDSCs could suppress T cell proliferation and promote CRC cell growth via cell-to-cell contact. Such effects could be abolished by the inhibition of oxidative metabolism, including the production of nitric oxide (NO), and reactive oxygen species (ROS).ConclusionsOur results reveal the functional interdependence between MDSCs, T cells and cancer cells in CRC pathogenesis. Understanding the impact of MDSCs on T cells and tumor cells will be helpful to establish an immunotherapeutic strategy in CRC patients.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
6.2
作者：
Lafata, JE;Williams, LK;Divine, G
通讯作者：
Divine, G
影响因子：
11.2
作者：
Halama, Niels;Michel, Sara;Jaeger, Dirk
通讯作者：
Jaeger, Dirk
影响因子：
11.2
作者：
Rodriguez PC;Ernstoff MS;Hernandez C;Atkins M;Zabaleta J;Sierra R;Ochoa AC
通讯作者：
Ochoa AC
影响因子：
2.2
作者：
Kotsakis, Athanasios;Harasymczuk, Malgorzata;Schilling, Bastian;Georgoulias, Vasilis;Argiris, Athanassios;Whiteside, Theresa L.
通讯作者：
Whiteside, Theresa L.