Dataset Information

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

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.

SUBMITTER: Huang Q

PROVIDER: S-EPMC7867134 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Huang Qiutong Q Jacquelot Nicolas N Preaudet Adele A Hediyeh-Zadeh Soroor S Souza-Fonseca-Guimaraes Fernando F McKenzie Andrew N J ANJ Hansbro Philip M PM Davis Melissa J MJ Mielke Lisa A LA Putoczki Tracy L TL Belz Gabrielle T GT

Cancers 20210201 3

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 ...[more]

PMID: 33535624

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Project description:BackgroundRecent studies have shown patient-derived tumor organoids can predict the drug response of patients with cancer. However, the prognostic value of patient-derived tumor organoid-based drug tests in predicting the progression-free survival of patients with stage IV colorectal cancer after surgery remains unknown.ObjectiveThis study aimed to explore the prognostic value of patient-derived tumor organoid-based drug tests in patients with stage IV colorectal cancer after surgery.DesignRetrospective cohort study.SettingsSurgical samples were obtained from patients with stage IV colorectal cancer at the Nanfang Hospital.PatientsA total of 108 patients who underwent surgery with successful patient-derived tumor organoid culture and drug testing were recruited between June 2018 and June 2019.InterventionsPatient-derived tumor organoid culture and chemotherapeutic drug testing.Main outcomes measuresProgression-free survival.ResultsAccording to the patient-derived tumor organoid-based drug test, 38 patients were drug sensitive and 76 patients were drug resistant. The median progression-free survival was 16.0 months in the drug-sensitive group and 9.0 months in the drug resistant group ( p < 0.001). Multivariate analyses showed that drug resistance (HR, 3.38; 95% CI, 1.84-6.21; p < 0.001), right-sided colon (HR, 3.50; 95% CI, 1.71-7.15; p < 0.001), mucinous adenocarcinoma (HR, 2.47; 95% CI, 1.34-4.55; p = 0.004), and non-R0 resection (HR, 2.70; 95% CI, 1.61-4.54; p < 0.001) were independent predictors of progression-free survival. The new patient-derived tumor organoid-based drug test model, which includes the patient-derived tumor organoid-based drug test, primary tumor location, histological type, and R0 resection, was more accurate than the traditional clinicopathological model in predicting progression-free survival ( p = 0.001).LimitationsA single-center cohort study.ConclusionsPatient-derived tumor organoids can predict progression-free survival in patients with stage IV colorectal cancer after surgery. Patient-derived tumor organoid drug resistance is associated with shorter progression-free survival, and the addition of patient-derived tumor organoid drug tests to existing clinicopathological models improves the ability to predict progression-free survival.

Dataset Information

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

Publications

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

Similar Datasets

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