Blockade of the B7-H1/PD-1 Pathway for Cancer Immunotherapy

Blockade of the B7-H1/PD-1 Pathway for Cancer Immunotherapy
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DOI:
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发表时间:
2011-12
期刊:
The Yale Journal of Biology and Medicine
影响因子:
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通讯作者:
D. Flies;Britt J. Sandler;M. Sznol;Lieping Chen
D. Flies;Britt J. Sandler;M. Sznol;Lieping Chen
中科院分区:
其他
文献类型:
--
作者:
D. Flies;Britt J. Sandler;M. Sznol;Lieping Chen

文献摘要

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The aim of cancer immunotherapy is to treat malignant disease by inducing or enhancing cancer specific immune responses. With the identification of tumor-associated antigens (TAAs) in the 1990s, cancer immunotherapy research largely focused on inducing immune responses against TAAs but achieved limited success. More recently, the underlying mechanisms and molecular pathways that cancers manipulate to subvert immune-mediated destruction have been identified, including a set of molecules with potent coinhibitory functions. Coinhibitory molecules are expressed on the surface of immune cells, cancer cells, and stromal cells and negatively regulate immune responses to cancer. In particular, one of these ligand-receptor coinhibitory interactions, B7-H1/PD-1, is critical for modulating immune responses to cancer. This knowledge led to the design of revolutionary new immunotherapeutics based on the manipulation of these molecular pathways. Monoclonal antibodies (mAbs) are the primary immunotherapeutic modality used to promote immune function via antagonism or agonism of inhibitory or stimulatory molecular pathways, respectively. Here, we review current knowledge on the function of the B7-H1/PD-1 pathway in mice and humans, its role in the subversion of immune responses in cancer, and clinical evidence that mAb targeting of this pathway results in profound immune anti-cancer effects.