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Oncotarget. 2015 Aug 14;6(23):19393-404.

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.

Sui X1,2,3, Ma J4, Han W1,2, Wang X1,2, Fang Y1,2, Li D1, Pan H1,2,3, Zhang L3,5.

Author information

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
Department of Gastrointestinal Surgery, Nankai Hospital, Nankai District, Tianjin, China.
5
Transplantation Institute and Toronto General Research Institute, University Health Network, Toronto, ON, Canada.

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.

KEYWORDS:

PD-1; PD-L1; cancer; checkpoint inhibitor; immunotherapy

PMID:
26305724
PMCID:
PMC4637293
DOI:
10.18632/oncotarget.5107
[Indexed for MEDLINE]
Free PMC Article

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