Oncotarget

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The anticancer immune response of anti-PD-1/PD-L1 and the genetic determinants of response to anti-PD-1/PD-L1 antibodies in cancer patients

Xinbing Sui, Junhong Ma, Weidong Han, Xian Wang, Yong Fang, Da Li, Hongming Pan and Li Zhang _

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Oncotarget. 2015; 6:19393-19404. https://doi.org/10.18632/oncotarget.5107

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Abstract

Xinbing Sui1,2,3,*, Junhong Ma5,*, Weidong Han1,2, Xian Wang1,2, Yong Fang1,2, Da Li1, Hongming Pan1,2,3 and Li Zhang3,4

1 Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China

2 Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China

3 Department of Immunology, University of Toronto, Toronto, ON, Canada

4 Transplantation Institute and Toronto General Research Institute, University Health Network, Toronto, Canada

5 Department of Gastrointestinal Surgery, Nankai Hospital, Nankai District, Tianjin, China

* These authors have contributed equally to this work

Correspondence to:

Hongming Pan, email:

Li Zhang, email:

Keywords: PD-1, PD-L1, cancer, checkpoint inhibitor, immunotherapy

Received: May 26, 2015 Accepted: July 08, 2015 Published: August 05, 2015

Abstract

The programmed death-1 (PD-1), a coinhibitory receptor expressed on activated T cells and B cells, is demonstrated to induce an immune-mediated response and play a critical role in tumor initiation and development. The cancer patients harboring PD-1 or PD ligand 1 (PD-L1) protein expression have often a poor prognosis and clinical outcome. Currently, targeting PD-1 pathway as a potential new anticancer strategy is attracting more and more attention in cancer treatment. Several monoclonal antibodies against PD-1 or PD-L1 have been reported to enhance anticancer immune responses and induce tumor cell death. Nonetheless, the precise molecular mechanisms by which PD-1 affects various cancers remain elusive. Moreover, this therapy is not effective for all the cancer patients and only a fraction of patients respond to the antibodies targeting PD-1 or PD-L1, indicating these antibodies may only works in a subset of certain cancers. Thus, understanding the novel function of PD-1 and genetic determinants of response to anti-PD-1 therapy will allow us to develop a more effective and individualized immunotherapeutic strategy for cancer.


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