Multiregion single-cell sequencing reveals the transcriptional landscape of the immune microenvironment of colorectal cancer

多区域单细胞测序揭示结直肠癌免疫微环境的转录景观

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作者:Wei Wang, Yu Zhong, Zhenkun Zhuang, Jiarui Xie, Yueer Lu, Chengzhi Huang, Yan Sun, Liang Wu, Jianhua Yin, Hang Yu, Zhiqiang Jiang, Shanshan Wang, Chunqing Wang, Yuanhang Zhang, Yilin Huang, Chongyin Han, Zhenggang Zhong, Jialin Hu, Ying Ouyang, Huisheng Liu, Mengya Yu, Xiaochan Wei, Dandan Chen, Liz

Abstract

The tumor microenvironment is a complex ecosystem formed by distinct and interacting cell populations, and its composition is related to cancer prognosis and response to clinical treatment. In this study, we have taken the advantage of two single-cell RNA sequencing technologies (Smart-seq2 and DNBelab C4) to generate an atlas of 15,115 immune and nonimmune cells from primary tumors and hepatic metastases of 18 colorectal cancer (CRC) patients. We observed extensive changes in the proportions and functional states of T cells and B cells in tumor tissues, compared to those of paired non-tumor tissues. Importantly, we found that B cells from early CRC tumor were identified to be pre-B like expressing tumor suppressors, whereas B cells from advanced CRC tumors tended to be developed into plasma cells. We also identified the association of IgA+ IGLC2+ plasma cells with poor CRC prognosis, and demonstrated a significant interaction between B-cell and myeloid-cell signaling, and found CCL8+ cycling B cells/CCR5+ T-cell interactions as a potential antitumoral mechanism in advanced CRC tumors. Our results provide deeper insights into the immune infiltration within CRC, and a new perspective for the future research in immunotherapies for CRC.

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