Wang Hongxia, Pezeshki Abdul Mohammad, Yu Xiaofei, Guo Chunqing, Subjeck John R, Wang Xiang-Yang
Department of Human Molecular Genetics, Virginia Commonwealth University , Richmond, VA , USA.
Department of Cell Stress Biology, Roswell Park Cancer Institute , Buffalo, NY , USA.
Front Oncol. 2015 Jan 12;4:377. doi: 10.3389/fonc.2014.00377. eCollection 2014.
Glucose-regulated protein 170 (GRP170) is the largest member of glucose-regulated protein family that resides in the endoplasmic reticulum (ER). As a component of the ER chaperone network, GRP170 assists in protein folding, assembly, and transportation of secretory or transmembrane proteins. The well documented cytoprotective activity of intracellular GRP170 due to its intrinsic chaperoning property has been shown to provide a survival benefit in cancer cells during tumor progression or metastasis. Accumulating evidence shows that extracellular GRP170 displays a superior capacity in delivering tumor antigens to specialized antigen-presenting cells for cross-presentation, resulting in generation of an anti-tumor immune response dependent on cytotoxic CD8(+) T cells. This unique feature of GRP170 provides a molecular basis for using GRP170 as an immunostimulatory adjuvant to develop a recombinant vaccine for therapeutic immunization against cancers. This review summarizes the latest findings in understanding the biological effects of GRP170 on cell functions and tumor progression. The immunomodulating activities of GRP170 during interactions with the innate and adaptive arms of the immune system as well as its therapeutic applications in cancer immunotherapy will be discussed.
葡萄糖调节蛋白170（GRP170）是位于内质网（ER）中的葡萄糖调节蛋白家族的最大成员。作为内质网伴侣网络的一个组成部分，GRP170协助分泌性或跨膜蛋白的折叠、组装和运输。细胞内GRP170因其内在的伴侣特性而具有充分记录的细胞保护活性，已被证明在肿瘤进展或转移过程中为癌细胞提供生存益处。越来越多的证据表明，细胞外GRP170在将肿瘤抗原递送至专门的抗原呈递细胞进行交叉呈递方面表现出卓越的能力，从而导致依赖细胞毒性CD8(+) T细胞产生抗肿瘤免疫反应。GRP170的这一独特特性为将GRP170用作免疫刺激佐剂以开发用于癌症治疗性免疫接种的重组疫苗提供了分子基础。本综述总结了在理解GRP170对细胞功能和肿瘤进展的生物学效应方面的最新发现。将讨论GRP170在与免疫系统的固有和适应性分支相互作用期间的免疫调节活性及其在癌症免疫治疗中的治疗应用。
