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.

中文翻译：

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结直肠癌进展过程中肿瘤浸润先天淋巴细胞的转分化。


先天淋巴细胞 (ILC) 驻留在粘膜表面，可增强免疫反应、维持粘膜完整性并维持组织稳态。然而，肿瘤浸润性 ILC 如何调节肿瘤的发生和进展尚不清楚。在这里，我们通过单细胞 RNA 测序分析了结直肠癌 (CRC) 进展过程中的肿瘤浸润 ILC。我们鉴定出六簇具有独特特征的肿瘤浸润 ILC。 ILC1在CRC晚期表达抑制性受体并经历抑制性功能转换。 ILC2被分为三个子集（称为ILC2-A、-B、-C），其中ILC2-C子集可以促进肿瘤进展。 HS3ST1和PD1在晚期CRC肿瘤的ILC2中高表达，并且ILC2中HS3ST1或PD1的缺乏抑制了肿瘤生长。此外，ILC3在CRC进展过程中转分化为ILCreg，并且ILCreg促进肿瘤生长。值得注意的是，TGF-β信号传导启动了ILC3向ILCreg的转化，而阻断TGF-β信号传导可以破坏ILCreg转分化并抑制肿瘤生长。因此，干预 ILC 转化可能是 CRC 免疫治疗的潜在策略。