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PMID: 22437870 Published · epublish English Journal Article Research Support, Non-U.S. Gov't Review

The blockade of immune checkpoints in cancer immunotherapy.

Nature reviews. Cancer ·Vol. 12 ·No. 4 ·2012-03-22 ·Pages 252-64

Pardoll DM

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.

MeSH Terms
Animals Antigens, Neoplasm/immunology,metabolism CTLA-4 Antigen/physiology Cancer Vaccines/therapeutic use Clinical Trials as Topic Humans Immunotherapy Molecular Targeted Therapy Neoplasms/immunology,metabolism,therapy Programmed Cell Death 1 Receptor/physiology Tumor Escape
Chemicals
Antigens, Neoplasm CTLA-4 Antigen CTLA4 protein, human Cancer Vaccines PDCD1 protein, human Programmed Cell Death 1 Receptor
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Pardoll Drew M
Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, CRB1 Room 444, 1650 Orleans Street, Baltimore, Maryland 21287, USA. [email protected]
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Article Info
Journal
Nature reviews. Cancer
Abbr.
Nat Rev Cancer
ISSN
1474-1768
DOI
10.1038/nrc3239
Email
[email protected]
Published
2012-03-22
Epub
2012-00-22
Pages
252-64
Language
English
Region
England
NLM ID
101124168
PMCID
PMC4856023
Subset
IM
Grants
NCI NIH HHS · P30 CA006973 · United States
NCI NIH HHS · P30 CA021765 · United States
External Links
PubMed source DOI: 10.1038/nrc3239 PMC Full Text View journal details
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