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

Huang, Qiutong; Jacquelot, Nicolas; Preaudet, Adele; Hediyeh-zadeh, Soroor; Souza-Fonseca-Guimaraes, Fernando; McKenzie, Andrew N. J.; Hansbro, Philip M.; Davis, Melissa J.; Mielke, Lisa A.; Putoczki, Tracy L.; Belz, Gabrielle T.

doi:10.3390/cancers13030559

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

^1,2,

^1,2

^1,2,

^1,2,

Fernando Souza-Fonseca-Guimaraes

Andrew N. J. McKenzie

⁴,

⁵

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and

Gabrielle T. Belz

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Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne 3052, Australia

Department of Medical Biology, University of Melbourne, Parkville, Melbourne 3010, Australia

The University of Queensland Diamantina Institute, 37 Kent Street, Woolloongabba, Brisbane 4102, Australia

⁴

Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK

⁵

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

⁶

Department of Clinical Pathology, University of Melbourne, Parkville, Melbourne 3010, Australia

⁷

Olivia Newton-John Cancer Research Institute, La Trobe University School of Cancer Medicine, Heidelberg 3084, Australia

Author to whom correspondence should be addressed.

Academic Editor: Lorenzo Moretta

Cancers 2021, 13(3), 559; https://doi.org/10.3390/cancers13030559

Received: 4 January 2021 / Revised: 25 January 2021 / Accepted: 27 January 2021 / Published: 1 February 2021

(This article belongs to the Special Issue NK/ILCs in Tumors)

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Colorectal cancer is the second leading cause of cancer-related death worldwide. The immune system plays a key role in controlling tumour onset and development. However, our immune system is complex and includes many different cell types which differently impact colorectal cancer outcomes. In this study, we investigated the function of the specialised type 2 innate lymphoid cells (ILC2) in colorectal cancer development and progression. We found that ILC2 infiltrate colorectal tumours and their presence was associated with reduced tumour burden in mice. In patients, this infiltration correlated with improved overall survival. Collectively, our work reveals that ILC2s are beneficial to colorectal cancer outcomes.

Abstract

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. View Full-Text

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

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MDPI and ACS Style

Huang, Q.; Jacquelot, N.; Preaudet, A.; Hediyeh-zadeh, S.; Souza-Fonseca-Guimaraes, F.; McKenzie, A.N.J.; Hansbro, P.M.; Davis, M.J.; Mielke, L.A.; Putoczki, T.L.; Belz, G.T. Type 2 Innate Lymphoid Cells Protect against Colorectal Cancer Progression and Predict Improved Patient Survival. Cancers 2021, 13, 559. https://doi.org/10.3390/cancers13030559

AMA Style

Huang Q, Jacquelot N, Preaudet A, Hediyeh-zadeh S, Souza-Fonseca-Guimaraes F, McKenzie ANJ, Hansbro PM, Davis MJ, Mielke LA, Putoczki TL, Belz GT. Type 2 Innate Lymphoid Cells Protect against Colorectal Cancer Progression and Predict Improved Patient Survival. Cancers. 2021; 13(3):559. https://doi.org/10.3390/cancers13030559

Chicago/Turabian Style

Huang, Qiutong, Nicolas Jacquelot, Adele Preaudet, Soroor Hediyeh-zadeh, Fernando Souza-Fonseca-Guimaraes, Andrew N.J. McKenzie, Philip M. Hansbro, Melissa J. Davis, Lisa A. Mielke, Tracy L. Putoczki, and Gabrielle T. Belz. 2021. "Type 2 Innate Lymphoid Cells Protect against Colorectal Cancer Progression and Predict Improved Patient Survival" Cancers 13, no. 3: 559. https://doi.org/10.3390/cancers13030559

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

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