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      The blockade of immune checkpoints in cancer immunotherapy.

      1
      Nature reviews. Cancer
      Springer Science and Business Media LLC

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          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.

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          Author and article information

          Journal
          Nat Rev Cancer
          Nature reviews. Cancer
          Springer Science and Business Media LLC
          1474-1768
          1474-175X
          Mar 22 2012
          : 12
          : 4
          Affiliations
          [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
          Article
          NIHMS779907 nrc3239
          10.1038/nrc3239
          4856023
          22437870
          f962b41e-8fae-4e94-8ac7-683cfd81b441
          History

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