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Immunotherapy. 2014;6(4):459-75. doi: 10.2217/imt.14.9.

Harnessing the power of the immune system via blockade of PD-1 and PD-L1: a promising new anticancer strategy.

Author information

1
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Cancer Research Building I, Room 186, 401 North Broadway Street, Baltimore, MD 21287, USA.

Abstract

Cancer cells employ several mechanisms to evade the immune system of their host, thus escaping immune recognition and elimination. Of particular interest is a cancer cell's ability to co-opt the immune system's innate ligands and inhibitory receptors (also known as checkpoints), thus creating an immunosuppressive microenvironment that downregulates T-cell activation and cell signaling. The recent development of the checkpoint inhibitors anti-programmed death-1 and anti-programmed death ligand-1 has generated an enormous amount of interest as a potential new anticancer strategy in solid tumors, particularly in non-small-cell lung cancer, renal cell carcinoma and melanoma. Data suggest significant disease response rates using anti-programmed death-1 and anti-programmed death ligand-1 antibodies, even in heavily pretreated patients. Future directions include optimization of drug delivery sequence and combination of immunotherapy with other therapies including cytotoxic chemotherapy, radiation, antiangiogenic agents and small-molecule tyrosine kinase inhibitors.

PMID:
24815784
PMCID:
PMC4732706
DOI:
10.2217/imt.14.9
[Indexed for MEDLINE]
Free PMC Article

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