The blockade of immune checkpoints in cancer immunotherapy

被引:10761
作者
Pardoll, Drew M. [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA
关键词
T-CELL-ACTIVATION; PROGRAMMED DEATH-1 LIGAND-1; B7; FAMILY; INDOLEAMINE 2,3-DIOXYGENASE; DEXTRO-1-METHYL TRYPTOPHAN; INHIBITORY RECEPTORS; METASTATIC MELANOMA; ANTITUMOR IMMUNITY; PROGNOSTIC-FACTORS; ANTIBODY BLOCKADE;
D O I
10.1038/nrc3239
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:252 / 264
页数:13
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