The blockade of immune checkpoints in cancer immunotherapy

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)252-264
Number of pages13
JournalNature Reviews Cancer
Volume12
Issue number4
DOIs
StatePublished - Apr 2012

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Immunotherapy
Programmed Cell Death 1 Receptor
Immunity
CTLA-4 Antigen
Ligands
Self Tolerance
Drug Approval
Antibodies
Neoplasm Antigens
Immune System
Neoplasms
T-Lymphocytes
Food
Proteins
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The blockade of immune checkpoints in cancer immunotherapy. / Pardoll, Andrew Mark.

In: Nature Reviews Cancer, Vol. 12, No. 4, 04.2012, p. 252-264.

Research output: Contribution to journalArticle

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