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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784864967687667712
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
work_keys_str_mv AT yamadakota reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT saitomasafumi reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT andomasayuki reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT abetomoki reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT mukoyamatomosuke reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT agawakyosuke reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT watanabeakihiro reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT takamurashiki reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT fujitamitsugu reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT urakawanaoki reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT hasegawahiroshi reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT kanajishingo reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT matsudatakeru reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT oshikiritaro reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT kakejiyoshihiro reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression
AT yamashitakimihiro reducednumberandimmunedysfunctionofcd4tcellsinobesityacceleratecolorectalcancerprogression