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...
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MDPI AG
2022-12-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/1/86 |
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| author | Kota Yamada Masafumi Saito Masayuki Ando Tomoki Abe Tomosuke Mukoyama Kyosuke Agawa Akihiro Watanabe Shiki Takamura Mitsugu Fujita Naoki Urakawa Hiroshi Hasegawa Shingo Kanaji Takeru Matsuda Taro Oshikiri Yoshihiro Kakeji Kimihiro Yamashita |
| author_facet | Kota Yamada Masafumi Saito Masayuki Ando Tomoki Abe Tomosuke Mukoyama Kyosuke Agawa Akihiro Watanabe Shiki Takamura Mitsugu Fujita Naoki Urakawa Hiroshi Hasegawa Shingo Kanaji Takeru Matsuda Taro Oshikiri Yoshihiro Kakeji Kimihiro Yamashita |
| author_sort | Kota Yamada |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T10:05:38Z |
| format | Article |
| id | doaj.art-2c390a3cf8a344239940b22a31cd4849 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T10:05:38Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2c390a3cf8a344239940b22a31cd48492023-11-16T15:05:54ZengMDPI AGCells2073-44092022-12-011218610.3390/cells12010086Reduced Number and Immune Dysfunction of CD4+ T Cells in Obesity Accelerate Colorectal Cancer ProgressionKota Yamada0Masafumi Saito1Masayuki Ando2Tomoki Abe3Tomosuke Mukoyama4Kyosuke Agawa5Akihiro Watanabe6Shiki Takamura7Mitsugu Fujita8Naoki Urakawa9Hiroshi Hasegawa10Shingo Kanaji11Takeru Matsuda12Taro Oshikiri13Yoshihiro Kakeji14Kimihiro Yamashita15Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, JapanDepartment of Disaster and Emergency and Critical Care Medicine, Graduate School of Medicine, Kobe University, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, JapanDepartment of Immunology, Kindai University Faculty of Medicine, 377-2 Ono-higashi, Osakasayama 589-0014, JapanCenter for Medical Education and Clinical Training, Kindai University Faculty of Medicine, 377-2 Onohigashi, Osaka 589-0014, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, JapanDivision of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, JapanObesity, 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.https://www.mdpi.com/2073-4409/12/1/86obesitycolorectal cancerhigh-fat dietCD4+ T celltumor immune microenvironment |
| spellingShingle | Kota Yamada Masafumi Saito Masayuki Ando Tomoki Abe Tomosuke Mukoyama Kyosuke Agawa Akihiro Watanabe Shiki Takamura Mitsugu Fujita Naoki Urakawa Hiroshi Hasegawa Shingo Kanaji Takeru Matsuda Taro Oshikiri Yoshihiro Kakeji Kimihiro Yamashita Reduced Number and Immune Dysfunction of CD4+ T Cells in Obesity Accelerate Colorectal Cancer Progression Cells obesity colorectal cancer high-fat diet CD4+ T cell tumor immune microenvironment |
| 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 | obesity colorectal cancer high-fat diet CD4+ T cell tumor immune microenvironment |
| url | https://www.mdpi.com/2073-4409/12/1/86 |
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