Reduced Number and Immune Dysfunction of CD4+ T Cells in Obesity Accelerate Colorectal Cancer Progression
Obesity, a known risk factor for various types of cancer, reduces the number and function of cytotoxic immune cells in the tumor immune microenvironment (TIME). However, the impact of obesity on CD4+ T cells remains unclear. Therefore, this study aimed to clarify the impact of obesity on CD4+ T cell...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818365/ https://www.ncbi.nlm.nih.gov/pubmed/36611881 http://dx.doi.org/10.3390/cells12010086 |
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author | Yamada, Kota Saito, Masafumi Ando, Masayuki Abe, Tomoki Mukoyama, Tomosuke Agawa, Kyosuke Watanabe, Akihiro Takamura, Shiki Fujita, Mitsugu Urakawa, Naoki Hasegawa, Hiroshi Kanaji, Shingo Matsuda, Takeru Oshikiri, Taro Kakeji, Yoshihiro Yamashita, Kimihiro |
author_facet | Yamada, Kota Saito, Masafumi Ando, Masayuki Abe, Tomoki Mukoyama, Tomosuke Agawa, Kyosuke Watanabe, Akihiro Takamura, Shiki Fujita, Mitsugu Urakawa, Naoki Hasegawa, Hiroshi Kanaji, Shingo Matsuda, Takeru Oshikiri, Taro Kakeji, Yoshihiro Yamashita, Kimihiro |
author_sort | Yamada, Kota |
collection | PubMed |
description | Obesity, a known risk factor for various types of cancer, reduces the number and function of cytotoxic immune cells in the tumor immune microenvironment (TIME). However, the impact of obesity on CD4+ T cells remains unclear. Therefore, this study aimed to clarify the impact of obesity on CD4+ T cells in the TIME. A tumor-bearing obese mouse model was established by feeding with 45% high-fat diet (HFD), followed by inoculation with a colon cancer cell line MC38. Tumor growth was significantly accelerated compared to that in mice fed a control diet. Tumor CD4+ T cells showed a significant reduction in number and an increased expression of programmed death-1 (PD-1), and decreased CD107a expression and cytokine such as IFN-γ and TNF-α production, indicating dysfunction. We further established CD4+ T cell-depleted HFD-fed model mice, which showed reduced tumor infiltration, increased PD-1 expression in CD8+ T cells, and obesity-induced acceleration of tumor growth in a CD4+ T cell-dependent manner. These findings suggest that the reduced number and dysfunction of CD4+ T cells due to obesity led to a decreased anti-tumor response of both CD4+ and CD8+ T cells to ultimately accelerate the progression of colorectal cancer. Our findings may elucidate the pathogenesis for poor outcomes of colorectal cancer associated with obesity. |
format | Online Article Text |
id | pubmed-9818365 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98183652023-01-07 Reduced Number and Immune Dysfunction of CD4+ T Cells in Obesity Accelerate Colorectal Cancer Progression Yamada, Kota Saito, Masafumi Ando, Masayuki Abe, Tomoki Mukoyama, Tomosuke Agawa, Kyosuke Watanabe, Akihiro Takamura, Shiki Fujita, Mitsugu Urakawa, Naoki Hasegawa, Hiroshi Kanaji, Shingo Matsuda, Takeru Oshikiri, Taro Kakeji, Yoshihiro Yamashita, Kimihiro Cells Article Obesity, a known risk factor for various types of cancer, reduces the number and function of cytotoxic immune cells in the tumor immune microenvironment (TIME). However, the impact of obesity on CD4+ T cells remains unclear. Therefore, this study aimed to clarify the impact of obesity on CD4+ T cells in the TIME. A tumor-bearing obese mouse model was established by feeding with 45% high-fat diet (HFD), followed by inoculation with a colon cancer cell line MC38. Tumor growth was significantly accelerated compared to that in mice fed a control diet. Tumor CD4+ T cells showed a significant reduction in number and an increased expression of programmed death-1 (PD-1), and decreased CD107a expression and cytokine such as IFN-γ and TNF-α production, indicating dysfunction. We further established CD4+ T cell-depleted HFD-fed model mice, which showed reduced tumor infiltration, increased PD-1 expression in CD8+ T cells, and obesity-induced acceleration of tumor growth in a CD4+ T cell-dependent manner. These findings suggest that the reduced number and dysfunction of CD4+ T cells due to obesity led to a decreased anti-tumor response of both CD4+ and CD8+ T cells to ultimately accelerate the progression of colorectal cancer. Our findings may elucidate the pathogenesis for poor outcomes of colorectal cancer associated with obesity. MDPI 2022-12-25 /pmc/articles/PMC9818365/ /pubmed/36611881 http://dx.doi.org/10.3390/cells12010086 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yamada, Kota Saito, Masafumi Ando, Masayuki Abe, Tomoki Mukoyama, Tomosuke Agawa, Kyosuke Watanabe, Akihiro Takamura, Shiki Fujita, Mitsugu Urakawa, Naoki Hasegawa, Hiroshi Kanaji, Shingo Matsuda, Takeru Oshikiri, Taro Kakeji, Yoshihiro Yamashita, Kimihiro Reduced Number and Immune Dysfunction of CD4+ T Cells in Obesity Accelerate Colorectal Cancer Progression |
title | Reduced Number and Immune Dysfunction of CD4+ T Cells in Obesity Accelerate Colorectal Cancer Progression |
title_full | Reduced Number and Immune Dysfunction of CD4+ T Cells in Obesity Accelerate Colorectal Cancer Progression |
title_fullStr | Reduced Number and Immune Dysfunction of CD4+ T Cells in Obesity Accelerate Colorectal Cancer Progression |
title_full_unstemmed | Reduced Number and Immune Dysfunction of CD4+ T Cells in Obesity Accelerate Colorectal Cancer Progression |
title_short | Reduced Number and Immune Dysfunction of CD4+ T Cells in Obesity Accelerate Colorectal Cancer Progression |
title_sort | reduced number and immune dysfunction of cd4+ t cells in obesity accelerate colorectal cancer progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818365/ https://www.ncbi.nlm.nih.gov/pubmed/36611881 http://dx.doi.org/10.3390/cells12010086 |
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