Increased adiposity enhances the accumulation of MDSCs in the tumor microenvironment and adipose tissue of pancreatic tumor-bearing mice and in immune organs of tumor-free hosts

William J. Turbitt, Shawntawnee D. Collins, Huicui Meng, Connie J. Rogers

Research output: Contribution to journalArticle

Abstract

Obesity is associated with increased risk and reduced survival for many types of cancer. Increasing adiposity may affect the balance between immunosuppressive and antitumor mechanisms critical for dictating cancer progression or remission. The goal of the current study was to determine if increased adiposity altered tumor growth, survival, and myeloid-derived suppressor cell (MDSC) accumulation in a subcutaneous murine model of pancreatic cancer. C57BL/6 mice were placed on a 30% kcal calorie-restricted diet, 10% kcal from fat diet fed ad libitum, or 60% kcal from fat diet fed ad libitum for 16 weeks to generate lean, overweight, and obese mice, respectively; followed by subcutaneous injection with 1 × 106 Panc.02 cells. We observed a significant linear relationship between increased adiposity and increased tumor growth and mortality; increased accumulation of Gr-1+CD11b+ MDSCs; and reduced CD8 T cell:MDSC ratio in multiple tissues, including tumor. Increased adiposity also increased the accumulation of MDSCs in the spleen and lymph node of tumor-free mice. These data suggest adiposity induces MDSC accumulation, which may contribute to an immunosuppressive environment promoting tumor growth. Overall, our findings provide a rationale to prevent or reverse increased body weight as a strategy to reduce the accumulation of immunosuppressive cell types.

Original languageEnglish (US)
Article number3012
JournalNutrients
Volume11
Issue number12
DOIs
StatePublished - Dec 2019

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Tumor Microenvironment
Adiposity
adiposity
adipose tissue
Adipose Tissue
neoplasms
suppressor cells
immunosuppressive agents
mice
Immunosuppressive Agents
Neoplasms
Diet
Growth
Fats
pancreatic neoplasms
Obese Mice
low calorie diet
remission
subcutaneous injection
Subcutaneous Injections

All Science Journal Classification (ASJC) codes

  • Food Science
  • Nutrition and Dietetics

Cite this

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title = "Increased adiposity enhances the accumulation of MDSCs in the tumor microenvironment and adipose tissue of pancreatic tumor-bearing mice and in immune organs of tumor-free hosts",
abstract = "Obesity is associated with increased risk and reduced survival for many types of cancer. Increasing adiposity may affect the balance between immunosuppressive and antitumor mechanisms critical for dictating cancer progression or remission. The goal of the current study was to determine if increased adiposity altered tumor growth, survival, and myeloid-derived suppressor cell (MDSC) accumulation in a subcutaneous murine model of pancreatic cancer. C57BL/6 mice were placed on a 30{\%} kcal calorie-restricted diet, 10{\%} kcal from fat diet fed ad libitum, or 60{\%} kcal from fat diet fed ad libitum for 16 weeks to generate lean, overweight, and obese mice, respectively; followed by subcutaneous injection with 1 × 106 Panc.02 cells. We observed a significant linear relationship between increased adiposity and increased tumor growth and mortality; increased accumulation of Gr-1+CD11b+ MDSCs; and reduced CD8 T cell:MDSC ratio in multiple tissues, including tumor. Increased adiposity also increased the accumulation of MDSCs in the spleen and lymph node of tumor-free mice. These data suggest adiposity induces MDSC accumulation, which may contribute to an immunosuppressive environment promoting tumor growth. Overall, our findings provide a rationale to prevent or reverse increased body weight as a strategy to reduce the accumulation of immunosuppressive cell types.",
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Increased adiposity enhances the accumulation of MDSCs in the tumor microenvironment and adipose tissue of pancreatic tumor-bearing mice and in immune organs of tumor-free hosts. / Turbitt, William J.; Collins, Shawntawnee D.; Meng, Huicui; Rogers, Connie J.

In: Nutrients, Vol. 11, No. 12, 3012, 12.2019.

Research output: Contribution to journalArticle

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