Linkage of CD8+ T cell exhaustion with high-fat diet-induced tumourigenesis

Abstract Obesity increases the risk of cancer. Increased levels of hormones (such as oestrogen, insulin, insulin-like growth factor, and leptin), free fatty acid-induced production of reactive oxygen species, an altered intestinal microbiome and chronic inflammation are known to be associated with a...

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Autores principales:	Tomonobu Kado, Allah Nawaz, Akiko Takikawa, Isao Usui, Kazuyuki Tobe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/85ab8330adc8478fa09fdf2f9cf97c8e
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spelling	oai:doaj.org-article:85ab8330adc8478fa09fdf2f9cf97c8e2021-12-02T15:08:47ZLinkage of CD8+ T cell exhaustion with high-fat diet-induced tumourigenesis10.1038/s41598-019-48678-02045-2322https://doaj.org/article/85ab8330adc8478fa09fdf2f9cf97c8e2019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48678-0https://doaj.org/toc/2045-2322Abstract Obesity increases the risk of cancer. Increased levels of hormones (such as oestrogen, insulin, insulin-like growth factor, and leptin), free fatty acid-induced production of reactive oxygen species, an altered intestinal microbiome and chronic inflammation are known to be associated with an increased cancer risk in obese subjects. However, the mechanism underlying the connection between obesity and cancer development remains elusive. Here, we show that a high-fat diet (HFD) promotes tumour initiation/progression and induces a phenotypic switch from PD-1− CD8+ non-exhausted T cells to PD-1+ CD8+ exhausted T cells in a murine breast cancer model. While PD-1− CD8+ non-exhausted T cells predominated in the mammary glands of normal diet (ND)-fed mice, PD-1+ CD8+ exhausted T cells accumulated in the developing tumours of HFD-fed mice. Gene expression profiles indicated that PD-1+ CD8+ T cells expressed higher levels of the tumour-trophic gene Opn and lower levels of the cytotoxic genes Ifng and Gzmb than did PD-1− CD8+ T cells. Our study provides a possible mechanistic linkage between obesity and cancer.Tomonobu KadoAllah NawazAkiko TakikawaIsao UsuiKazuyuki TobeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-8 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tomonobu Kado Allah Nawaz Akiko Takikawa Isao Usui Kazuyuki Tobe Linkage of CD8+ T cell exhaustion with high-fat diet-induced tumourigenesis
description	Abstract Obesity increases the risk of cancer. Increased levels of hormones (such as oestrogen, insulin, insulin-like growth factor, and leptin), free fatty acid-induced production of reactive oxygen species, an altered intestinal microbiome and chronic inflammation are known to be associated with an increased cancer risk in obese subjects. However, the mechanism underlying the connection between obesity and cancer development remains elusive. Here, we show that a high-fat diet (HFD) promotes tumour initiation/progression and induces a phenotypic switch from PD-1− CD8+ non-exhausted T cells to PD-1+ CD8+ exhausted T cells in a murine breast cancer model. While PD-1− CD8+ non-exhausted T cells predominated in the mammary glands of normal diet (ND)-fed mice, PD-1+ CD8+ exhausted T cells accumulated in the developing tumours of HFD-fed mice. Gene expression profiles indicated that PD-1+ CD8+ T cells expressed higher levels of the tumour-trophic gene Opn and lower levels of the cytotoxic genes Ifng and Gzmb than did PD-1− CD8+ T cells. Our study provides a possible mechanistic linkage between obesity and cancer.
format	article
author	Tomonobu Kado Allah Nawaz Akiko Takikawa Isao Usui Kazuyuki Tobe
author_facet	Tomonobu Kado Allah Nawaz Akiko Takikawa Isao Usui Kazuyuki Tobe
author_sort	Tomonobu Kado
title	Linkage of CD8+ T cell exhaustion with high-fat diet-induced tumourigenesis
title_short	Linkage of CD8+ T cell exhaustion with high-fat diet-induced tumourigenesis
title_full	Linkage of CD8+ T cell exhaustion with high-fat diet-induced tumourigenesis
title_fullStr	Linkage of CD8+ T cell exhaustion with high-fat diet-induced tumourigenesis
title_full_unstemmed	Linkage of CD8+ T cell exhaustion with high-fat diet-induced tumourigenesis
title_sort	linkage of cd8+ t cell exhaustion with high-fat diet-induced tumourigenesis
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/85ab8330adc8478fa09fdf2f9cf97c8e
work_keys_str_mv	AT tomonobukado linkageofcd8tcellexhaustionwithhighfatdietinducedtumourigenesis AT allahnawaz linkageofcd8tcellexhaustionwithhighfatdietinducedtumourigenesis AT akikotakikawa linkageofcd8tcellexhaustionwithhighfatdietinducedtumourigenesis AT isaousui linkageofcd8tcellexhaustionwithhighfatdietinducedtumourigenesis AT kazuyukitobe linkageofcd8tcellexhaustionwithhighfatdietinducedtumourigenesis
_version_	1718388009969123328

Linkage of CD8+ T cell exhaustion with high-fat diet-induced tumourigenesis

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