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
Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Melbourne 3010, Australia.
Cancers (Basel). 2021 Feb 1;13(3):559. doi: 10.3390/cancers13030559.
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）的慢性炎症会促进结直肠癌（CRC）的进展。虽然适应性T细胞在结直肠癌中的作用现已明确，但固有免疫细胞，特别是固有淋巴细胞（ILCs）的作用尚不清楚。为了确定ILCs在结直肠癌中的作用，我们采用了互补的异位和化学诱导的结直肠癌小鼠模型。我们发现ILCs在结直肠癌肿瘤中大量存在，并有助于抗肿瘤免疫。我们聚焦于ILC2，结果显示，与同窝野生型对照相比，ILC2缺陷小鼠的肿瘤负担更高。我们生成了一个ILC2基因特征，并使用机器学习模型发现，肿瘤内ILC2基因特征高的结直肠癌患者具有良好的临床预后。总的来说，我们的结果突出了ILC2在结直肠癌中的关键作用，提示通过基于ILC2激动剂的治疗方法改善临床结局的潜在新途径。
