Peritoneal metastasis is a leading cause of death in gastrointestinal cancers. This study characterizes single-cell transcriptomes of ascites cancer/immune cells from 35 gastric cancer patients, revealing increased pro-angiogenic monocyte-like dendritic cells with reduced antigen-presenting capacity, correlating with poor prognosis. Therapy-induced evolution of these cells and regulatory/proliferative T cells is described, along with high-plasticity gastric cancer clusters prone to shifting to a high-proliferative phenotype via paligenosis. Autophagy-related genes (MARCKS and TXNIP) mark high-plasticity cancer with poor prognosis, and autophagy inhibitors induce apoptosis in patient-derived organoids. These findings offer insights into cancer/immune cell trajectories underlying metastasis progression and therapy resistance.
Publisher
Nature Communications
Published On
Feb 14, 2023
Authors
Xuan-Zhang Huang, Min-Jiao Pang, Jia-Yi Li, Han-Yu Chen, Jing-Xu Sun, Yong-Xi Song, Hong-Jie Ni, Shi-Yu Ye, Shi Bai, Teng-Hui Li, Xin-Yu Wang, Jing-Yuan Lu, Jin-Jia Yang, Xun Sun, Jason C. Mills, Zhi-Feng Miao, Zhen-Ning Wang
Tags
peritoneal metastasis
gastric cancer
immune cells
angiogenic dendritic cells
autophagy
prognosis
therapeutic resistance
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