Type 2 Innate Lymphoid Cells Protect against Colorectal Cancer Progression and Predict Improved Patient Survival

Cancers

卷:13

Philip M. Hansbro¹  Andrew N.J. McKenzie²  Fernando Souza-Fonseca-Guimaraes³  Nicolas Jacquelot⁴  Adele Preaudet⁴  Gabrielle T. Belz⁴  Soroor Hediyeh-zadeh⁴  Lisa A. Mielke⁴  Qiutong Huang⁴  Melissa J. Davis⁴  Tracy L. Putoczki⁴ 

[1] Center for Inflammation, Centenary Institute and the School of Life Sciences, University of Technology Sydney, Sydney 2050, Australia;

[2] Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK;

[3] University of Queensland Diamantina Institute, 37 Kent Street, Woolloongabba, Brisbane 4102, Australia;

[4] Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne 3052, Australia;

关键词: colon cancer;    colitis-associated cancer;    ILC2;    IL-5;    IL-13;    inflammation;   

DOI  :  10.3390/cancers13030559

来源: DOAJ

【 摘 要 】

Chronic inflammation of the gastrointestinal (GI) tract contributes to colorectal cancer (CRC) progression. While the role of adaptive T cells in CRC is now well established, the role of innate immune cells, specifically innate lymphoid cells (ILCs), is not well understood. To define the role of ILCs in CRC we employed complementary heterotopic and chemically-induced CRC mouse models. We discovered that ILCs were abundant in CRC tumours and contributed to anti-tumour immunity. We focused on ILC2 and showed that ILC2-deficient mice developed a higher tumour burden compared with littermate wild-type controls. We generated an ILC2 gene signature and using machine learning models revealed that CRC patients with a high intratumor ILC2 gene signature had a favourable clinical prognosis. Collectively, our results highlight a critical role for ILC2 in CRC, suggesting a potential new avenue to improve clinical outcomes through ILC2-agonist based therapeutic approaches.

【 授权许可】

Unknown