Zhang JP, Yan BZ, Liu J, Wang W. Action of circulating and infiltrating B cells in the immune microenvironment of colorectal cancer by single-cell sequencing analysis. World J Gastrointest Oncol 2024; 16(6): 2683-2696 [DOI: 10.4251/wjgo.v16.i6.2683]
Corresponding Author of This Article
Wei Wang, MD, Doctor, Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Hebei Medical University, No. 89 Donggang Road, Yuhua District, Shijiazhuang 050032, Hebei Province, China. 10707514@qq.com
Research Domain of This Article
Medicine, Research & Experimental
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Jun 15, 2024; 16(6): 2683-2696 Published online Jun 15, 2024. doi: 10.4251/wjgo.v16.i6.2683
Action of circulating and infiltrating B cells in the immune microenvironment of colorectal cancer by single-cell sequencing analysis
Jing-Po Zhang, Bing-Zheng Yan, Jie Liu, Wei Wang
Jing-Po Zhang, Bing-Zheng Yan, Wei Wang, Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Hebei Medical University, Shijiazhuang 050032, Hebei Province, China
Jie Liu, Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital, Changsha 410002, Hunan Province, China
Author contributions: Zhang JP wrote the manuscript; Yan BZ and Liu J collected the data; Wang W conceived and guided the study. All authors reviewed, edited, and approved the final manuscript and revised it critically for important intellectual content, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Hunan Provincial People`s Hospital.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at email: 10707514@qq.com.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei Wang, MD, Doctor, Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Hebei Medical University, No. 89 Donggang Road, Yuhua District, Shijiazhuang 050032, Hebei Province, China. 10707514@qq.com
Received: December 12, 2023 Revised: March 10, 2024 Accepted: April 9, 2024 Published online: June 15, 2024 Processing time: 185 Days and 13.1 Hours
Abstract
BACKGROUND
The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer (CRC), one of the most prevalent malignancies worldwide. In this study, multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC. By revealing the heterogeneity and functional differences of B cells in cancer immunity, we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies.
AIM
To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC, explore the potential driving mechanism of B cell development, analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules, and search for possible regulatory pathways to promote the anti-tumor effects of B cells.
METHODS
A total of 69 paracancer (normal), tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database (https://portal.gdc.cancer.gov/). After the immune cells were sorted by multicolor flow cytometry, the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform, and the data were analyzed using bioinformatics tools such as Seurat. The differences in the number and function of B cell infiltration between tumor and normal tissue, the interaction between B cell subsets and T cells and myeloid cell subsets, and the transcription factor regulatory network of B cell subsets were explored and analyzed.
RESULTS
Compared with normal tissue, the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly. Among them, germinal center B cells (GCB) played the most prominent role, with positive clone expansion and heavy chain mutation level increasing, and the trend of differentiation into memory B cells increased. However, the number of plasma cells in the tumor microenvironment decreased significantly, and the plasma cells secreting IgA antibodies decreased most obviously. In addition, compared with the immune microenvironment of normal tissues, GCB cells in tumor tissues became more closely connected with other immune cells such as T cells, and communication molecules that positively regulate immune function were significantly enriched.
CONCLUSION
The role of GCB in CRC tumor microenvironment is greatly enhanced, and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level. Meanwhile, GCB has enhanced its association with immune cells in the microenvironment, which plays a positive anti-tumor effect.
Core Tip: To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of colorectal cancer (CRC), explore the potential driving mechanism of B cell development, analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules, and search for possible regulatory pathways to promote the anti-tumor effects of B cells. The role of germinal center B cells in CRC tumor microenvironment is greatly enhanced, and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level.
