CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China.
Cell Res. 2020 Jul;30(7):610-622. doi: 10.1038/s41422-020-0312-y. Epub 2020 May 4.
Innate lymphoid cells (ILCs) reside in mucosal surfaces to potentiate immune responses, sustain mucosal integrity and maintain tissue homeostasis. However, how tumor infiltrating ILCs modulate tumor development and progression is unclear. Here we profiled tumor infiltrating ILCs during colorectal cancer (CRC) progression by single-cell RNA sequencing. We identified six clusters of tumor infiltrating ILCs with unique features. ILC1s expressed inhibitory receptors and underwent inhibitory functional conversion at the late stage of CRC. ILC2s were classified into three subsets (called ILC2-A, -B, -C), of which ILC2-C subset could facilitate tumor progression. HS3ST1 and PD1 were highly expressed in ILC2s of late stage CRC tumors and deficiency of HS3ST1 or PD1 in ILC2s suppressed tumor growth. Moreover, ILC3s transdifferentiated into ILCregs during CRC progression and ILCregs promoted tumor growth. Of note, TGF-β signaling initiated the conversion of ILC3s to ILCregs and blockade of TGF-β signaling could disrupt the ILCreg transdifferentiation and inhibited tumor growth. Thus, intervention of ILC conversions might be a potential strategy for CRC immunotherapy.
固有淋巴细胞 (ILCs) 存在于黏膜表面，以增强免疫反应、维持黏膜完整性和维持组织内稳态。然而，肿瘤浸润的 ILCs 如何调节肿瘤的发生和发展尚不清楚。在这里，我们通过单细胞 RNA 测序对结直肠癌 (CRC) 进展过程中的肿瘤浸润性 ILCs 进行了分析。我们鉴定了六个具有独特特征的肿瘤浸润性 ILC 簇。ILC1s 表达抑制性受体，并在 CRC 的晚期发生抑制性功能转换。ILC2s 分为三个亚群（称为 ILC2-A、-B、-C），其中 ILC2-C 亚群可以促进肿瘤进展。HS3ST1 和 PD1 在晚期 CRC 肿瘤的 ILC2s 中高表达，ILC2s 中 HS3ST1 或 PD1 的缺失抑制了肿瘤生长。此外，ILC3s 在 CRC 进展过程中向 ILCregs 转化，ILCregs 促进肿瘤生长。值得注意的是，TGF-β 信号启动了 ILC3s 向 ILCregs 的转化，阻断 TGF-β 信号可以破坏 ILCreg 的转化并抑制肿瘤生长。因此，干预 ILC 转化可能是 CRC 免疫治疗的一种潜在策略。
