Single-cell RNA sequencing reveals that the immunosuppression landscape induced by chronic stress promotes colorectal cancer metastasis

单细胞 RNA 测序揭示慢性应激引起的免疫抑制环境促进结直肠癌转移

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作者:Yingru Zhang, Ying Feng, Yiyang Zhao, Yuanyuan Feng, Mengyao Li, Wenkai Wang, Zhongya Ni, Huirong Zhu, Yan Wang

Abstract

The high prevalence of depressive disorders in individuals with cancer and their contribution to tumour progression is a topic that is gradually gaining attention. Recent evidence has shown that there are prominent connections between immune gene variants and mood disorders. The homeostasis of the tumour immune microenvironment (TIME) and the infiltration and activation of immune cells play a very important role in the antitumour effect. In this study, we established a compound mouse model with chronic unpredictable mild stress (CUMS) and orthotopic colorectal cancer to simulate colorectal cancer (CRC) patients with depression. Using 10✕Genomics single-cell transcriptome sequencing technology, we profiled nearly 30,000 cells from tumour samples of 8 mice from the control and CUMS groups, revealed that immune cells in tumours under a chronic stress state trend toward a more immunosuppressive and exhaustive status, and described the crosstalk between the overall inflammatory environment and immunosuppressive landscape to provide mechanistic information or efficacious strategies for immune-oncology treatments in CRC with depressive disorders.

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