Mechanisms of Hypoxia-Mediated Immune Escape in Cancer
Mechanisms of Hypoxia-Mediated Immune Escape in Cancer
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DOI：
10.1158/0008-5472.can-14-2598
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发表时间：
2014-12-15
期刊：
影响因子：
11.2
通讯作者：
Graham, Charles H.
中科院分区：
文献类型：
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作者：
Barsoum, Ivraym B.;Koti, Madhuri;Graham, Charles H.
恶性进展的一个重要方面是肿瘤细胞获得避免免疫系统识别和破坏的能力（免疫逃逸）。临床癌症进展还与肿瘤缺氧的发展相关，其在机制上与癌细胞中恶性表型的获得相关。尽管低氧在肿瘤细胞侵袭和转移以及对治疗的抵抗中的作用已经得到了很好的证实，但相对较少的研究已经检查了低氧对癌症免疫逃逸的贡献。越来越多的证据表明，缺氧可以通过改变先天性和适应性免疫细胞的功能和/或通过增加肿瘤细胞对免疫效应物的细胞溶解活性的内在抗性来损害抗癌免疫。在这里，我们讨论了缺氧对肿瘤免疫逃逸的贡献的某些方面，并为环磷酸鸟苷（cGMP）信号转导在缺氧诱导的免疫逃逸的调节中的新作用提供了证据。因此，我们认为癌细胞中cGMP信号的激活可能具有重要的免疫学应用。（C）2014年AACR。
An important aspect of malignant progression is the acquired ability of tumor cells to avoid recognition and destruction by the immune system (immune escape). Clinical cancer progression is also associated with the development of tumor hypoxia, which is mechanistically linked to the acquisition of malignant phenotypes in cancer cells. Despite the well-established role of hypoxia in tumor cell invasion and metastasis, and resistance to therapy, relatively few studies have examined the contribution of hypoxia to cancer immune escape. Accumulating evidence reveals that hypoxia can impair anticancer immunity by altering the function of innate and adaptive immune cells and/or by increasing the intrinsic resistance of tumor cells to the cytolytic activity of immune effectors. Here, we discuss certain aspects of the contribution of hypoxia to tumor immune escape and provide evidence for a novel role of cyclic guanosine monophosphate (cGMP) signaling in the regulation of hypoxia-induced immune escape. Thus, we propose that activation of cGMP signaling in cancer cells may have important immunotherapeutic applications. (C)2014 AACR.