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

2 型先天淋巴細(xì)胞可預(yù)防結(jié)直腸癌進(jìn)展并預(yù)測患者生存率的提高

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.

結(jié)直腸癌是全球癌癥相關(guān)死亡的第二大原因。免疫系統(tǒng)在控制腫瘤的發(fā)生和發(fā)展中起關(guān)鍵作用。然而，我們的免疫系統(tǒng)很復(fù)雜，包括許多不同的細(xì)胞類型，它們對結(jié)直腸癌的結(jié)果有不同的影響。在這項(xiàng)研究中，我們調(diào)查了特化的 2 型先天淋巴細(xì)胞 (ILC2) 在結(jié)直腸癌發(fā)展和進(jìn)展中的功能。我們發(fā)現(xiàn) ILC2 浸潤結(jié)直腸腫瘤，并且它們的存在與小鼠腫瘤負(fù)荷的減少有關(guān)。在患者中，這種浸潤與改善的總體生存率相關(guān)?？偟膩碚f，我們的工作表明 ILC2 對結(jié)直腸癌的預(yù)后有益。

高效搖瓶

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.

胃腸道 (GI) 的慢性炎癥有助于結(jié)直腸癌 (CRC) 的進(jìn)展。雖然適應(yīng)性 T 細(xì)胞在 CRC 中的作用現(xiàn)已得到充分確立，但先天免疫細(xì)胞，特別是先天淋巴細(xì)胞 (ILC) 的作用尚不清楚。為了確定 ILC 在 CRC 中的作用，我們采用了互補(bǔ)的異位和化學(xué)誘導(dǎo)的 CRC 小鼠模型。我們發(fā)現(xiàn) ILC 在 CRC 腫瘤中含量豐富，并有助于抗腫瘤免疫。我們專注于 ILC2，并表明與同窩野生型對照相比，ILC2 缺陷小鼠的腫瘤負(fù)荷更高。我們生成了 ILC2 基因特征，并使用機(jī)器學(xué)習(xí)模型顯示具有高腫瘤內(nèi) ILC2 基因特征的 CRC 患者具有良好的臨床預(yù)后。

三角細(xì)胞搖瓶

Colorectal cancer is associated with an increase in cytokine-producing ILC2s in the colon and these cells are protective against the development of colorectal cancer. Furthermore, an ILC2 gene signature in patient samples is associated with increased survival. This is a novel finding, highlighting the protective role of ILC2s in CRC and is a promising new diagnostic tool to help identify patients with a higher probability of survival.

結(jié)直腸癌與結(jié)腸中產(chǎn)生細(xì)胞因子的 ILC2 的增加有關(guān)，這些細(xì)胞對結(jié)直腸癌的發(fā)展具有保護(hù)作用。此外，患者樣本中的 ILC2 基因特征與增加的存活率有關(guān)。這是一項(xiàng)新發(fā)現(xiàn)，強(qiáng)調(diào)了 ILC2 在 CRC 中的保護(hù)作用，是一種很有前途的新診斷工具，可幫助識別具有更高生存概率的患者。

細(xì)胞培養(yǎng)板

關(guān)鍵詞： 結(jié)腸癌,結(jié)腸炎相關(guān)癌癥,ILC2,IL-5,IL-13,炎,colon cancer,colitis-associated cancer, ILC2, IL-5, IL-13, inflammation

來源：MDPI https://www.mdpi.com/2072-6694/13/3/559/htm