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单细胞测序解析左、右侧结直肠癌的差异。

Resolving the difference between left-sided and right-sided colorectal cancer by single-cell sequencing.

机构信息

Department of Colorectal Surgery, Shandong University Qilu Hospital, Jinan, Shandong, China.

Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

出版信息

JCI Insight. 2022 Jan 11;7(1):e152616. doi: 10.1172/jci.insight.152616.

DOI:10.1172/jci.insight.152616
PMID:34793335
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8765049/
Abstract

Colorectal cancers (CRCs) exhibit differences in incidence, pathogenesis, molecular pathways, and outcome depending on the location of the tumor. The transcriptomes of 27,927 single human CRC cells from 3 left-sided and 3 right-sided CRC patients were profiled by single-cell RNA-Seq (scRNA-Seq). Right-sided CRC harbors a significant proportion of exhausted CD8+ T cells of a highly migratory nature. One cluster of cells from left-sided CRC exhibiting states preceding exhaustion and a high ratio of preexhausted/exhausted T cells were favorable prognostic markers. Notably, we identified a potentially novel RBP4+NTS+ subpopulation of cancer cells that exclusively expands in left-sided CRC. Tregs from left-sided CRC showed higher levels of immunotherapy-related genes than those from right-sided CRC, indicating that left-sided CRC may have increased responsiveness to immunotherapy. Antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) induced by M2-like macrophages were more pronounced in left-sided CRC and correlated with a good prognosis in CRC.

摘要

结直肠癌（CRC）的发病率、发病机制、分子途径和预后因肿瘤位置而异。通过单细胞 RNA-Seq（scRNA-Seq）对 3 名左侧和 3 名右侧 CRC 患者的 27927 个人类 CRC 单细胞转录组进行了分析。右侧 CRC 含有大量具有高迁移性的耗竭 CD8+T 细胞。从左侧 CRC 中发现了一个表现出衰竭前状态和高比例的预耗竭/耗竭 T 细胞的细胞簇，是有利的预后标志物。值得注意的是，我们鉴定了一种可能的新型 RBP4+NTS+癌细胞亚群，其仅在左侧 CRC 中扩增。与右侧 CRC 相比，左侧 CRC 的 Treg 显示出更高水平的免疫治疗相关基因，这表明左侧 CRC 可能对免疫治疗有更高的反应性。M2 样巨噬细胞诱导的抗体依赖的细胞吞噬作用（ADCP）和抗体依赖的细胞细胞毒性（ADCC）在左侧 CRC 中更为明显，并与 CRC 的良好预后相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/94cef51eeb23/jciinsight-7-152616-g086.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/d318e2cfd878/jciinsight-7-152616-g078.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/3412d2eba418/jciinsight-7-152616-g079.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/168d967b0297/jciinsight-7-152616-g080.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/2df618b12d67/jciinsight-7-152616-g081.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/99a5530d0c1f/jciinsight-7-152616-g082.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/23d289d28305/jciinsight-7-152616-g083.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/a89de54dc736/jciinsight-7-152616-g084.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/06aeb9734640/jciinsight-7-152616-g085.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/94cef51eeb23/jciinsight-7-152616-g086.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/d318e2cfd878/jciinsight-7-152616-g078.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/3412d2eba418/jciinsight-7-152616-g079.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/168d967b0297/jciinsight-7-152616-g080.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/2df618b12d67/jciinsight-7-152616-g081.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/99a5530d0c1f/jciinsight-7-152616-g082.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/23d289d28305/jciinsight-7-152616-g083.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/a89de54dc736/jciinsight-7-152616-g084.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/06aeb9734640/jciinsight-7-152616-g085.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b629/8765049/94cef51eeb23/jciinsight-7-152616-g086.jpg

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