期刊
IMMUNITY
卷 53, 期 6, 页码 1215-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2020.10.020
关键词
-
类别
资金
- Cancer Research UK Institute Award [A19258]
- EMBO long-term fellowship [ALTF-69-2016]
- EMBO advanced fellowship [aALTF-638-2018]
- National Institute for Health Research Manchester Biomedical Research Centre
- Society of Swedish Engineers in Great Britain
- Medical Research Council
- Cancer Research UK [FC001136]
- UK Medical Research Council [FC001136]
- Wellcome Trust [FC001136]
- ERC Advanced Investigator grant [AdG 268670]
- Wellcome Investigator Award [WT106973MA]
- Imperial Confidence in Concept Scheme [RSRO_P71752]
- Wellcome Trust Investigator Award [110091/Z/15/Z]
- Francis Crick Institute
- Wellcome Trust [110091/Z/15/Z] Funding Source: Wellcome Trust
Inflammation can support or restrain cancer progression and the response to therapy. Here, we searched for primary regulators of cancer-inhibitory inflammation through deep profiling of inflammatory tumor microenvironments (TMEs) linked to immune-dependent control in mice. We found that early intratumoral accumulation of interferon gamma (IFN-gamma)-producing natural killer (NK) cells induced a profound remodeling of the TME and unleashed cytotoxic T cell (CTL)-mediated tumor eradication. Mechanistically, tumor-derived prostaglandin E2 (PGE2) acted selectively on EP2 and EP4 receptors on NK cells, hampered the TME switch, and enabled immune evasion. Analysis of patient datasets across human cancers revealed distinct inflammatory TME phenotypes resembling those associated with cancer immune control versus escape in mice. This allowed us to generate a gene-expression signature that integrated opposing inflammatory factors and predicted patient survival and response to immune checkpoint blockade. Our findings identify features of the tumor inflammatory milieu associated with immune control of cancer and establish a strategy to predict immunotherapy outcomes.
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