IL-10 immunomodulation of myeloid cells regulates a murine model of ovarian cancer.
IL-10 immunomodulation of myeloid cells regulates a murine model of ovarian cancer.
复制标题
IL-10的髓样细胞免疫调节调节卵巢癌的鼠模型。
DOI：
10.3389/fimmu.2011.00029
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发表时间：
2011
影响因子：
7.3
通讯作者：
Berwin B
中科院分区：
文献类型：
--
作者：
Hart KM;Byrne KT;Molloy MJ;Usherwood EM;Berwin B
人卵巢癌微环境和卵巢癌小鼠模型中IL-10水平升高已得到充分证实，并与不良临床预后相关。然而，在众多的免疫抑制因子中，IL-10对卵巢肿瘤微环境的实际贡献、其作用机制及其可能的功能冗余尚不清楚。我们以前证明，消除卵巢肿瘤腹水中的髓源性抑制细胞（MDSC）隔室可抑制肿瘤进展，有趣的是，可显著降低局部IL-10水平。在这里，我们确定了一种新的途径，其中肿瘤浸润MDSC是IL-10的主要生产者，重要的是，需要它来发展其体内免疫抑制功能。重要的是，我们证明了IL-10的作用是至关重要的，而不是多余的其他免疫抑制分子，在体内肿瘤进展：IL-10信号网络的阻断导致减轻MDSC介导的免疫抑制，改变T细胞表型和活性，并提高生存。这些研究将IL-10定义为卵巢肿瘤微环境中MDSC和T细胞的基本调节剂。重要的是，IL-10信号传导被证明是发展和维持容许肿瘤微环境所必需的，并且代表了抗肿瘤策略的可行靶标。
Elevated levels of IL-10 in the microenvironment of human ovarian cancer and murine models of ovarian cancer are well established and correlate with poor clinical prognosis. However, amongst a myriad of immunosuppressive factors, the actual contribution of IL-10 to the ovarian tumor microenvironment, the mechanisms by which it acts, and its possible functional redundancy are unknown. We previously demonstrated that elimination of the myeloid-derived suppressor cell (MDSC) compartment within the ovarian tumor ascites inhibited tumor progression and, intriguingly, significantly decreased local IL-10 levels. Here we identify a novel pathway in which the tumor-infiltrating MDSC are the predominant producers of IL-10 and, importantly, require it to develop their immunosuppressive function in vivo. Importantly, we demonstrate that the role of IL-10 is critical, and not redundant with other immunosuppressive molecules, to in vivo tumor progression: blockade of the IL-10 signaling network results in alleviation of MDSC-mediated immunosuppression, altered T cell phenotype and activity, and improved survival. These studies define IL-10 as a fundamental modulator of both MDSC and T cells within the ovarian tumor microenvironment. Importantly, IL-10 signaling is shown to be necessary to the development and maintenance of a permissive tumor microenvironment and represents a viable target for anti-tumor strategies.
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DOI：
10.4049/jimmunol.1000901
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lechner MG;Liebertz DJ;Epstein AL
通讯作者：
Epstein AL
影响因子：
5.8
作者：
Berger, S;Siegert, A;Hauptmann, S
通讯作者：
Hauptmann, S
DOI：
10.1073/pnas.0503726102
发表时间：
2005-07-05
影响因子：
11.1
作者：
Klebanoff, CA;Gattinoni, L;Restifo, NP
通讯作者：
Restifo, NP
影响因子：
4.8
作者：
Hart, Kevin M.;Bak, S. Peter;Berwin, Brent
通讯作者：
Berwin, Brent
影响因子：
20.3
作者：
Highfill, Steven L.;Rodriguez, Paulo C.;Blazar, Bruce R.
通讯作者：
Blazar, Bruce R.