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Nat Rev Cancer. 2012 Mar 22;12(4):252-64. doi: 10.1038/nrc3239.

The blockade of immune checkpoints in cancer immunotherapy.

Author information

1
Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, CRB1 Room 444, 1650 Orleans Street, Baltimore, Maryland 21287, USA. dpardol1@jhmi.edu

Abstract

Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.

PMID:
22437870
PMCID:
PMC4856023
DOI:
10.1038/nrc3239
[Indexed for MEDLINE]
Free PMC Article
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