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- Title
Reduced Number and Immune Dysfunction of CD4+ T Cells in Obesity Accelerate Colorectal Cancer Progression.
- Authors
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
- Abstract
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.
- Subjects
T cells; COLORECTAL cancer; CD4 antigen; CANCER invasiveness; HIGH-fat diet
- Publication
Cells (2073-4409), 2023, Vol 12, Issue 1, p86
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells12010086