Role of RAGE and Its Ligands on Inflammatory Responses to Brain Tumors.
Role of RAGE and Its Ligands on Inflammatory Responses to Brain Tumors.
复制标题
DOI：
10.3389/fncel.2021.770472
复制
发表时间：
2021
影响因子：
5.3
通讯作者：
Badie B
中科院分区：
文献类型：
--
作者：
Otazu GK;Dayyani M;Badie B
胶质瘤是最常见的脑癌形式，从生长相对缓慢的低级别到高度侵袭性的胶质母细胞瘤，尽管进行了多种模式的标准治疗，但中位总生存期仅为15个月。尽管使用检查点抑制剂的免疫疗法显著提高了一些癌症患者的存活率，但到目前为止，这些药物对恶性胶质瘤还没有显示出一致的疗效。因此，迫切需要更好地了解宿主炎症反应对这些耐药肿瘤新的免疫治疗方法的疗效的影响。RAGE是一种多配体模式识别受体，在糖尿病、阿尔茨海默病、囊性纤维化和癌症等各种炎症状态下被激活。在正常生理条件下，神经元、免疫细胞、活化的内皮细胞和血管平滑肌细胞中都有低水平的RAGE表达，但在慢性炎症中，由于其配体的积累，RAGE会过度表达。RAGE与一系列损伤相关的分子模式分子(DAMP)结合，包括AGEs、HMGB1、S100s和DNA，这些分子介导下游细胞反应，促进肿瘤生长、血管生成和侵袭。体外和体内研究都表明，抑制RAGE信号可以阻断炎症和癌症的进展和转移。在这里，我们将回顾我们目前对RAGE通路在胶质瘤进展中的作用的理解，以及如何利用它来提高免疫治疗方法的有效性。
Gliomas, the most common form of brain cancer, can range from relatively slow-growing low-grade to highly aggressive glioblastoma that has a median overall survival of only 15 months despite multimodal standard therapy. Although immunotherapy with checkpoint inhibitors has significantly improved patient survival for some cancers, to date, these agents have not shown consistent efficacy against malignant gliomas. Therefore, there is a pressing need to better understand the impact of host inflammatory responses on the efficacy of emerging immunotherapy approaches for these resistant tumors. RAGE is a multi-ligand pattern recognition receptor that is activated in various inflammatory states such as diabetes, Alzheimer’s disease, cystic fibrosis, and cancer. Low levels of RAGE can be found under normal physiological conditions in neurons, immune cells, activated endothelial, and vascular smooth muscle cells, but it is over-expressed under chronic inflammation due to the accumulation of its ligands. RAGE binds to a range of damage-associated molecular pattern molecules (DAMPs) including AGEs, HMGB1, S100s, and DNA which mediate downstream cellular responses that promote tumor growth, angiogenesis, and invasion. Both in vitro and in vivo studies have shown that inhibition of RAGE signaling can disrupt inflammation and cancer progression and metastasis. Here, we will review our current understanding of the role of RAGE pathway on glioma progression and how it could be exploited to improve the efficacy of immunotherapy approaches.
登录
查看更多内容
影响因子：
11.4
作者：
Erusalimsky JD
通讯作者：
Erusalimsky JD
影响因子：
4.6
作者：
Crowe, Lindsay A. N.;McLean, Michael;Millar, Neal L.
通讯作者：
Millar, Neal L.
影响因子：
3.9
作者：
Holla, F. K.;Postma, T. J.;Heimans, J. J.
通讯作者：
Heimans, J. J.
影响因子：
5.7
作者：
Hong, Bangxing;Muili, Kamaldeen;Kaur, Balveen
通讯作者：
Kaur, Balveen
影响因子：
1.1
作者：
Davis ME
通讯作者：
Davis ME