Molecular Pathways: Coexpression of Immune Checkpoint Molecules: Signaling Pathways and Implications for Cancer Immunotherapy
Molecular Pathways: Coexpression of Immune Checkpoint Molecules: Signaling Pathways and Implications for Cancer Immunotherapy
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DOI：
10.1158/1078-0432.ccr-12-1972
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发表时间：
2013-09-15
影响因子：
11.5
通讯作者：
Drake, Charles G.
中科院分区：
文献类型：
--
作者：
Nirschl, Christopher J.;Drake, Charles G.
免疫检查点分子在T细胞上的表达代表了免疫系统用来调节对自身蛋白质的反应的重要机制。检查点分子包括细胞毒性T淋巴细胞抗原-4、程序性死亡-1、淋巴细胞激活基因-3、T细胞免疫球蛋白和粘蛋白-3等。以前的研究已经确定了这些分子中的每一个单独的作用，但最近的数据表明，检查点分子的共同表达经常发生在癌症特异性T细胞和慢性感染的病原体特异性T细胞上。由于与每个检查点分子相关的信号通路尚未完全阐明，用特定的单抗阻断多个检查点可以改善几种慢性病毒感染以及广泛的癌症临床前模型的结果。最近的临床数据表明，转移性黑色素瘤患者也有类似的效果。这些发现支持单个免疫检查点分子可能通过不重叠的分子机制发挥作用的概念。在这里，我们回顾了关于免疫检查点分子信号和共表达的最新数据，包括在癌症和传染病中的信号和共表达，以及临床前和临床操作检查点蛋白的结果。(C)2013年AACR。
The expression of immune checkpoint molecules on T cells represents an important mechanism that the immune system uses to regulate responses to self-proteins. Checkpoint molecules include cytotoxic T lymphocyte antigen-4, programmed death-1, lymphocyte activation gene-3, T-cell immunoglobulin and mucin protein-3, and several others. Previous studies have identified individual roles for each of these molecules, but more recent data show that coexpression of checkpoint molecules occurs frequently on cancer-specific T cells as well as on pathogen-specific T cells in chronic infections. As the signaling pathways associated with each checkpoint molecule have not been fully elucidated, blocking multiple checkpoints with specific monoclonal antibodies results in improved outcomes in several chronic viral infections as well as in a wide array of preclinical models of cancer. Recent clinical data suggest similar effects in patients with metastatic melanoma. These findings support the concept that individual immune checkpoint molecules may function through nonoverlapping molecular mechanisms. Here, we review current data regarding immune checkpoint molecule signaling and coexpression, both in cancer and infectious disease, as well as the results of preclinical and clinical manipulations of checkpoint proteins. (C) 2013 AACR.