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<p>Obesity increases the risk of many cancers and impairs the anti-tumour immune response. However, little is known about whether the source or composition of dietary fat affects tumour growth or anti-tumour immunity in obesity. Here, we show that high-fat diets (HFDs) derived from lard, beef tallow or butter accelerate tumour growth in a syngeneic model of melanoma, but HFDs based on coconut oil, palm oil or olive oil do not, despite equivalent obesity. Using butter-based and palm oil-based HFDs as examples, we find that these dietary fat sources differentially regulate natural killer and CD8 T cell infiltration and function within the tumour microenvironment, governed by distinct effects on the plasma metabolome and intracellular metabolism. We identify diet-related lipid intermediates, namely long-chain acylcarnitine species, as immunosuppressive metabolites enriched in mice fed butter compared to palm oil HFD. Together, these results highlight the significance of diet in maintaining a healthy immune system and suggest that modifying dietary fat may improve cancer outcomes in obesity.</p>

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The source of dietary fat influences anti-tumour immunity in obese mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月25日

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  • Britta Kunkemoeller,
  • Hannah Prendeville,
  • Claire McIntyre,
  • Ayantu Temesgen,
  • Rόisín M. Loftus,
  • Conghui Yao,
  • Lydia Dyck,
  • Linda V. Sinclair,
  • Christina Rollings,
  • Aaron Douglas,
  • Gerard Pernes,
  • Kathleen A. J. Mitchelson,
  • Cathal Harmon,
  • Mathilde Raverdeau,
  • Ross Ward,
  • Harry Kane,
  • Jaclyn Kline,
  • Katie L. O’Brien,
  • Martin Brennan,
  • Frances Smith,
  • Brenneth Stevens,
  • Helen M. Roche,
  • Ed C. Lavelle,
  • David K. Finlay,
  • Doreen A. Cantrell,
  • Edward T. Chouchani,
  • Susan Kaech,
  • Evanna L. Mills,
  • Marcia Haigis,
  • Lydia Lynch

摘要

Obesity increases the risk of many cancers and impairs the anti-tumour immune response. However, little is known about whether the source or composition of dietary fat affects tumour growth or anti-tumour immunity in obesity. Here, we show that high-fat diets (HFDs) derived from lard, beef tallow or butter accelerate tumour growth in a syngeneic model of melanoma, but HFDs based on coconut oil, palm oil or olive oil do not, despite equivalent obesity. Using butter-based and palm oil-based HFDs as examples, we find that these dietary fat sources differentially regulate natural killer and CD8 T cell infiltration and function within the tumour microenvironment, governed by distinct effects on the plasma metabolome and intracellular metabolism. We identify diet-related lipid intermediates, namely long-chain acylcarnitine species, as immunosuppressive metabolites enriched in mice fed butter compared to palm oil HFD. Together, these results highlight the significance of diet in maintaining a healthy immune system and suggest that modifying dietary fat may improve cancer outcomes in obesity.