期刊
NATURE MEDICINE
卷 23, 期 3, 页码 368-375出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.4278
关键词
-
资金
- Knudson postdoctoral fellowship
- Cancer Research Institute/Irvington Institute
- Sistema Nacional de Investigacion (SNI) de SENACYT, Panama
- Princess Margaret Cancer Foundation
- Canada Foundation for Innovation
- Leaders Opportunity Fund [CFI 32383]
- Ontario Ministry of Research and Innovation, Ontario Research Fund Small Infrastructure Program
- Alexander von Humboldt Foundation [SKA2010]
- German Research Council [LA2558/3-1, LA2558/5-1, SFB974, RTG1949]
- US National Institutes of Health [AI066897, AI068129]
- Parker Institute for Cancer Immunotherapy
- Canada Research Chair in Autoimmunity and Tumor Immunity
- Canadian Institutes for Health Research [CCM 104887]
- CIHR Foundation [FDN143220]
Antitumor T cells are subject to multiple mechanisms of negative regulation(1-3). Recent findings that innate lymphoid cells (ILCs) regulate adaptive T cell responses(4-6) led us to examine the regulatory potential of ILCs in the context of cancer. We identified a unique ILC population that inhibits tumor -infiltrating lymphocytes (TILs) from high-grade serous tumors, defined their suppressive capacity in vitro, and performed a comprehensive analysis of their phenotype. Notably, the presence of this CD56+CD3- population in TIL cultures was associated with reduced T cell numbers, and further functional studies demonstrated that this population suppressed TIL expansion and altered TIL cytokine production. Transcriptome analysis and phenotypic characterization determined that regulatory CD56+CD3-cells exhibit low cytotoxic activity, produce IL-22, and have an expression profile that overlaps with those of natural killer (NK) cells and other ILCs. NKp46 was highly expressed by these cells, and addition of anti-NKp46 antibodies to TIL cultures abrogated the ability of these regulatory ILCs to suppress T cell expansion. Notably, the presence of these regulatory ILCs in TIL cultures corresponded with a striking reduction in the time to disease recurrence. These studies demonstrate that a previously uncharacterized ILC population regulates the activity and expansion of tumor-associated T cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据