肿瘤细胞治疗研究
英文原题：Tumor-infiltrating immature innate lymphoid cells in colorectal cancer are biased toward ILC1/tissue-resident NK cell differentiation.
Tumor-infiltrating immature innate lymphoid cells in colorectal cancer are biased toward ILC1/tissue-resident NK cell differentiation.
腹膜转移（PM）发生于10%的结直肠癌（CRC）患者中，并与不良预后相关。
腹膜转移（PM）发生于10%的结直肠癌（CRC）患者中，并与不良预后相关。尽管在CRC中已描述了失调的先天淋巴细胞（ILC），但其在CRC-PM中的功能仍不清楚。在此，我们使用单细胞RNA测序（11例患者）、流式细胞术（8例患者）和分化实验（24例患者）分析了CRC和CRC-PM患者的肿瘤样本。健康结肠、原发性CRC和CRC-PM肿瘤均被异质性的ILC3、ILC2、ILC1、组织驻留（tr）NK细胞和常规（c）NK细胞群体浸润。与健康结肠相比，原发性CRC和CRC-PM肿瘤中ILC3耗竭，但ILC1、trNK细胞和cNK细胞富集。CRC和CRC-PM肿瘤含有两个未成熟的ILC群体，即早期NK和初始（n）ILC，其中nILC在转录上偏向ILC1和trNK细胞。事实上，将分离的nILC与OP9-DL1细胞共培养可诱导肿瘤内nILC分化为ILC1/trNK样细胞。这些发现有助于理解CRC和CRC-PM的免疫发病机制，并为未来基于ILC1和NK细胞的治疗提供见解。
Peritoneal metastases (PM) occur in 10% of patients with colorectal cancer (CRC) and are linked to poor outcomes. Although dysregulated innate lymphoid cells (ILC) have been described in CRC, their function in CRC-PM remains unclear. Here, we analyze tumor samples from CRC and CRC-PM patients using single-cell RNA sequencing (11 patients), flow cytometry (8 patients) and differentiation assays (24 patients). Healthy colon, primary CRC and CRC-PM tumors are infiltrated by heterogeneous populations of ILC3, ILC2, ILC1, tissue resident (tr)NK cells and conventional (c)NK cells. Compared to healthy colons, primary CRC and CRC-PM tumors are depleted of ILC3 but enriched for ILC1, trNK cells and cNK cells. CRC and CRC-PM tumors harbor two immature ILC populations, early NK and naïve (n)ILC, with nILCs being transcriptionally skewed toward ILC1 and trNK cells. Indeed, co-culture of isolated nILCs with OP9-DL1 cells induces intratumoral nILC differentiation into ILC1/trNK-like cells. These findings help understand the immune pathogenesis of CRC and CRC-PM and provide insights for future ILC1 and NK cell-based therapies.
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