期刊
NATURE IMMUNOLOGY
卷 19, 期 7, 页码 723-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-018-0132-0
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资金
- Natural Science Foundation of China [81788101, 431570893, 81501355]
- Chinese Academy of Science [XDPB030301]
- Ministry of Science & Technology of China [2017ZX10203206003, 2017ZX10202203-002-001]
- Science and Technology Innovation Fund of Shenzhen [JCYJ20150521094519472, MX120150630114942288]
Checkpoint blockade enhances effector T cell function and has elicited long-term remission in a subset of patients with a broad spectrum of cancers. TIGIT is a checkpoint receptor thought to be involved in mediating T cell exhaustion in tumors; however, the relevance of TIGIT to the dysfunction of natural killer (NK) cells remains poorly understood. Here we found that TIGIT, but not the other checkpoint molecules CTLA-4 and PD-1, was associated with NK cell exhaustion in tumor-bearing mice and patients with colon cancer. Blockade of TIGIT prevented NK cell exhaustion and promoted NK cell-dependent tumor immunity in several tumor-bearing mouse models. Furthermore, blockade of TIGIT resulted in potent tumor-specific T cell immunity in an NK cell-dependent manner, enhanced therapy with antibody to the PD-1 ligand PD-L1 and sustained memory immunity in tumor re-challenge models. This work demonstrates that TIGIT constitutes a previously unappreciated checkpoint in NK cells and that targeting TIGIT alone or in combination with other checkpoint receptors is a promising anti-cancer therapeutic strategy.
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