2 型先天淋巴细胞可预防结直肠癌进展并预测患者生存率的提高

发表日期：2022-03-28

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

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.

结直肠癌是全球癌症相关死亡的第二大原因。免疫系统在控制肿瘤的发生和发展中起关键作用。然而，我们的免疫系统很复杂，包括许多不同的细胞类型，它们对结直肠癌的结果有不同的影响。在这项研究中，我们调查了特化的 2 型先天淋巴细胞 (ILC2) 在结直肠癌发展和进展中的功能。我们发现 ILC2 浸润结直肠肿瘤，并且它们的存在与小鼠肿瘤负荷的减少有关。在患者中，这种浸润与改善的总体生存率相关。总的来说，我们的工作表明 ILC2 对结直肠癌的预后有益。

高效摇瓶

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.

胃肠道 (GI) 的慢性炎症有助于结直肠癌 (CRC) 的进展。虽然适应性 T 细胞在 CRC 中的作用现已得到充分确立，但先天免疫细胞，特别是先天淋巴细胞 (ILC) 的作用尚不清楚。为了确定 ILC 在 CRC 中的作用，我们采用了互补的异位和化学诱导的 CRC 小鼠模型。我们发现 ILC 在 CRC 肿瘤中含量丰富，并有助于抗肿瘤免疫。我们专注于 ILC2，并表明与同窝野生型对照相比，ILC2 缺陷小鼠的肿瘤负荷更高。我们生成了 ILC2 基因特征，并使用机器学习模型显示具有高肿瘤内 ILC2 基因特征的 CRC 患者具有良好的临床预后。

三角细胞摇瓶

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.

结直肠癌与结肠中产生细胞因子的 ILC2 的增加有关，这些细胞对结直肠癌的发展具有保护作用。此外，患者样本中的 ILC2 基因特征与增加的存活率有关。这是一项新发现，强调了 ILC2 在 CRC 中的保护作用，是一种很有前途的新诊断工具，可帮助识别具有更高生存概率的患者。

细胞培养板