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J Immunol. 2017 May 1;198(9):3719-3728. doi: 10.4049/jimmunol.1602039. Epub 2017 Mar 27.

Characterization of the B Cell Receptor Repertoire in the Intestinal Mucosa and of Tumor-Infiltrating Lymphocytes in Colorectal Adenoma and Carcinoma.

Author information

1
BGI-Shenzhen, Shenzhen 518083, China.
2
Department of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Private University of Salzburg, 5110 Oberndorf, Austria.
3
American Medical Global Exchange, Sydney, New South Wales 2145, Australia; and.
4
First Department of Internal Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria.
5
Department of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Private University of Salzburg, 5110 Oberndorf, Austria; liuxiao@genomics.cn C.Datz@kh-oberndorf.at.
6
BGI-Shenzhen, Shenzhen 518083, China; liuxiao@genomics.cn C.Datz@kh-oberndorf.at.

Abstract

The B cells inhabited in mucosa play a vital role in mediating homeostasis with autoantigens and external Ags. Tumor-infiltrating lymphocytes are potential prognostic markers and therapeutic agents for cancer. However, the spatial heterogeneity of the B cell repertoire in intestinal mucosa and the tumor-infiltrating lymphocytes in colorectal cancer (CRC) remain poorly understood. In this study, we developed an unbiased method to amplify the IgH repertoire, as well as a bioinformatic pipeline to process these high-throughput sequencing data. With biopsies from seven intestinal mucosal segments, we uncovered their strong spatial homogeneity among the large intestine, where the clone overlap rate was up to 62.21%. The heterogeneity between terminal ileum and large intestine was also observed, including discrepant isotype distribution and low clone overlap rate. With tumor and adjacent normal mucosal tissues from CRC and colorectal advanced adenoma (AD) patients, we observed a similar IgH profile between tumor and adjacent normal mucosal tissues in AD, as well as a slight difference in CRC. Interestingly, we found distinct repertoire properties in the CRC tumor from AD and normal mucosa. Finally, we identified 1445 public clones for the normal mucosa, and 22 public clones for the CRC tumor with characteristic features. These data may be of potential use in clinical prognosis, diagnosis, and treatment of CRC.

PMID:
28348270
DOI:
10.4049/jimmunol.1602039
[Indexed for MEDLINE]
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