Hypoxia-driven immunosuppression: a new reason to use thermal therapy in the treatment of cancer?
Hypoxia-driven immunosuppression: a new reason to use thermal therapy in the treatment of cancer?
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DOI：
10.3109/02656731003601745
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Repasky EA
中科院分区：
文献类型：
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作者：
Lee CT;Mace T;Repasky EA
肿瘤微环境中的缺氧与放疗和化疗后的不良治疗结果以及癌症患者的总生存率降低相关。低氧支持肿瘤生长和干扰有效的放射和化学疗法的几种分子机制现在已经很好地建立。然而，几项新的研究指出了肿瘤微环境缺氧的另一个不祥结果：抑制抗肿瘤免疫效应细胞并增强肿瘤逃避免疫监视。这篇综述总结了这一重要信息，并强调了缺氧使几种不同类型的免疫效应细胞失能的机制数据，增强了免疫抑制细胞的活性，并提供了新的途径，有助于“盲”免疫细胞的肿瘤细胞的存在。最后，我们讨论的数据表明，温和的热疗法，通过其生理调节的能力，改变血管灌注和肿瘤微环境内的氧张力，以及它的能力，以提高功能的一些相同的免疫效应活动，被缺氧抑制，可用于快速安全地释放肿瘤微环境中的缺氧，从而减少更有效的免疫治疗的障碍。
Hypoxia within the tumor microenvironment is correlated with poor treatment outcome after radiation and chemotherapy, and with decreased overall survival in cancer patients. Several molecular mechanisms by which hypoxia supports tumor growth and interferes with effective radiation and chemotherapies are now well established. However, several new lines of investigation are pointing to yet another ominous outcome of hypoxia in the tumor microenvironment: suppression of anti-tumor immune effector cells and enhancement of tumor escape from immune surveillance. This review summarizes this important information, and highlights mechanistic data by which hypoxia incapacitates several different types of immune effector cells, enhances the activity of immunosuppressive cells and provides new avenues which help “blind” immune cells to the presence of tumor cells. Finally, we discuss data which indicates that mild thermal therapy, through its physiologically-regulated ability to alter vascular perfusion and oxygen tensions within the tumor microenvironment, as well as its ability to enhance the function of some of the same immune effector activities that are inhibited by hypoxia,, could be used to rapidly and safely release the tight grip of hypoxia in the tumor microenvironment thereby reducing barriers to more effective immune-based therapies.