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ID 119513
Author
Wang, Lifang Japanese Foundation for Cancer Research
Nagayama, Satoshi Japanese Foundation for Cancer Research|Uji-Tokusyukai Medical Center
Yamashita, Makiko Japanese Foundation for Cancer Research
Tate, Tomohiro Japanese Foundation for Cancer Research
Matsumoto, Saki Japanese Foundation for Cancer Research
Takamatsu, Manabu Japanese Foundation for Cancer Research
Kitano, Shigehisa Japanese Foundation for Cancer Research
Kiyotani, Kazuma Japanese Foundation for Cancer Research|National Institute of Biomedical Innovation, Health and Nutrition (NIBIOHN)
Nakamura, Yusuke Japanese Foundation for Cancer Research|National Institute of Biomedical Innovation, Health and Nutrition (NIBIOHN)
Keywords
CD8+ T cells
colorectal cancer
double-negative T cells
granzyme K
T cell receptor
Content Type
Journal Article
Description
TCRαβ+ CD4− CD8− double-negative T (DNT) cells are minor populations in peripheral blood, and their roles have mostly been discussed in inflammation and autoimmunity. However, the functions of DNT cells in tumor microenvironment remain to be elucidated. We investigated their characteristics, possible origins and functions in colorectal cancer tissues as well as their corresponding tumor-draining lymph nodes. We found a significant enrichment of DNT cells in tumor tissues compared with their corresponding lymph nodes, especially in tumors with lower T cell infiltration. T cell receptor (TCR) sequence analysis of CD4+ T, CD8+ T and DNT cells indicated that TCR sequences detected in DNT cells were found in CD8+ T cells, but rarely in CD4+ T cells, suggesting that a part of DNT cells was likely to be originated from CD8+ T cells. Through a single-cell transcriptomic analysis of DNT cells, we found that a DNT cell cluster, which showed similar phenotypes to central memory CD8+ T cells with low expression of effector and exhaustion markers, revealed some specific gene expression patterns, including higher GZMK expression. Moreover, in flow cytometry analysis, we found that DNT cells lost production of cytotoxic mediators. These findings imply that DNT cells might function as negative regulators of anti-tumor immune responses in tumor microenvironment.
Journal Title
OncoImmunology
ISSN
2162402X
Publisher
Taylor & Francis
Volume
13
Issue
1
Start Page
2373530
Published Date
2024-07-04
Rights
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
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DOI (Published Version)
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language
eng
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departments
University Hospital