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Morikawa R, Nemoto Y, Yonemoto Y, et al. Intraepithelial Lymphocytes Suppress Intestinal Tumor Growth by Cell-to-Cell Contact via CD103/E-Cadherin Signal. Cell Mol Gastroenterol Hepatol. 2021;11(5):1483-1503doi: 10.1016/j.jcmgh.2021.01.014.
Morikawa, R., Nemoto, Y., Yonemoto, Y., Tanaka, S., Takei, Y., Oshima, S., Nagaishi, T., Tsuchiya, K., Nozaki, K., Mizutani, T., Nakamura, T., Watanabe, M., & Okamoto, R. (2021). Intraepithelial Lymphocytes Suppress Intestinal Tumor Growth by Cell-to-Cell Contact via CD103/E-Cadherin Signal. Cellular and molecular gastroenterology and hepatology, 11(5), 1483-1503. https://doi.org/10.1016/j.jcmgh.2021.01.014
Morikawa, Ryo, et al. "Intraepithelial Lymphocytes Suppress Intestinal Tumor Growth by Cell-to-Cell Contact via CD103/E-Cadherin Signal." Cellular and molecular gastroenterology and hepatology vol. 11,5 (2021): 1483-1503. doi: https://doi.org/10.1016/j.jcmgh.2021.01.014
Morikawa R, Nemoto Y, Yonemoto Y, Tanaka S, Takei Y, Oshima S, Nagaishi T, Tsuchiya K, Nozaki K, Mizutani T, Nakamura T, Watanabe M, Okamoto R. Intraepithelial Lymphocytes Suppress Intestinal Tumor Growth by Cell-to-Cell Contact via CD103/E-Cadherin Signal. Cell Mol Gastroenterol Hepatol. 2021;11(5):1483-1503. doi: 10.1016/j.jcmgh.2021.01.014. Epub 2021 Jan 28. PMID: 33515805; PMCID: PMC8025200.
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Cell Mol Gastroenterol Hepatol. 2021;11(5):1483-1503. doi: 10.1016/j.jcmgh.2021.01.014. Epub 2021 Jan 28.

Intraepithelial Lymphocytes Suppress Intestinal Tumor Growth by Cell-to-Cell Contact via CD103/E-Cadherin Signal.

Cellular and molecular gastroenterology and hepatology

Ryo Morikawa, Yasuhiro Nemoto, Yuki Yonemoto, Shohei Tanaka, Yuria Takei, Shigeru Oshima, Takashi Nagaishi, Kiichiro Tsuchiya, Kengo Nozaki, Tomohiro Mizutani, Tetsuya Nakamura, Mamoru Watanabe, Ryuichi Okamoto

Affiliations

  1. Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
  2. Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan; Department of Advanced Therapeutics for GI Diseases, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: [email protected].
  3. Department of Advanced Therapeutics for GI Diseases, Tokyo Medical and Dental University, Tokyo, Japan.
  4. Department of Organoid Research and Development, Juntendo University, Tokyo, Japan.
  5. Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan; Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.

PMID: 33515805 PMCID: PMC8025200 DOI: 10.1016/j.jcmgh.2021.01.014

Abstract

BACKGROUND & AIMS: The reason why small intestinal cancer is rarer than colorectal cancer is not clear. We hypothesized that intraepithelial lymphocytes (IELs), which are enriched in the small intestine, are the closest immune cells to epithelial cells, exclude tumor cells via cell-to-cell contact.

METHODS: We developed DPE-green fluorescent protein (DPE-GFP) × adenomatous polyposis coli; multiple intestinal neoplasia (APC

RESULTS: In the small intestinal tumor microenvironment, T-cell movement was restricted around blood vessels and the frequency of interaction between IELs and epithelial cells was reduced. Genetic deletion of CD103 decreased the frequency of interaction between IELs and epithelial cells, and increased the number of small intestinal tumors. In the co-culture system, wild-type IELs expanded and infiltrated to intestinal tumor organoids from APC

CONCLUSIONS: The abundance of IELs in the small intestine may contribute to a low number of tumors, although this system may not work in the colon because of the sparseness of IELs. Strategies to increase the number of IELs in the colon or enhance cell-to-cell contact between IELs and epithelial cells may be effective for the prevention of intestinal tumors in patients with a high cancer risk.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: IELs; In Vivo Live Imaging; Organoid

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