Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived stem cell factor

作者：Chenchen Mao, Yanyu Chen, Dong Xing, Teming Zhang, Yangxuan Lin, Cong Long, Jiaye Yu, Yunhui Luo, Ming Tao, Wangkai Xie, Zheng Han, Dianfeng Mei, Dan Xiang, Mingdong Lu, Xian Shen, Xiangyang Xue · 发表于：eLife · 年份：2024 · DOI：10.7554/elife.97201 · 被引用次数：12 · 研究领域：Immune Cell Function and Interaction、Immune cells in cancer、Cancer Immunotherapy and Biomarkers

The abundance and biological contribution of natural killer (NK) cells in cancer are controversial. Here, we aim to uncover clinical relevance and cellular roles of NK cells in colon cancer liver metastasis (CCLM). Here, we integrated single-cell RNA-sequencing, spatial transcriptomics (ST), and bulk RNA-sequencing datasets to investigate NK cells' biological properties and functions in the microenvironment of primary and liver metastatic tumors. Results were validated through an in vitro co-culture experiment based on bioinformatics analysis. Useing single-cell RNA-sequencing and ST, we mapped the immune cellular landscape of colon cancer and well-matched liver metastatic cancer. We discovered that GZMK+ resting NK cells increased significantly in tumor tissues and were enriched in the tumor regions of both diseases. After combining bulk RNA and clinical data, we observed that these NK cell subsets contributed to a worse prognosis. Meanwhile, KIR2DL4+ activated NK cells exhibited the opposite position and relevance. Pseudotime cell trajectory analysis revealed the evolution of activated to resting NK cells. In vitro experiments further confirmed that tumor-cell-co-cultured NK cells exhibited a decidual-like status, as evidenced by remarkable increasing CD9 expression. Functional experiments finally revealed that NK cells exhibited tumor-activating characteristics by promoting the dissociation of SCF (stem cell factor) on the tumor cells membrane depending on cell-to-cell int...