[HTML][HTML] The blockade of immune checkpoints in cancer immunotherapy

DM Pardoll - Nature reviews cancer, 2012 - nature.com
Nature reviews cancer, 2012nature.com
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 …
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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