Abstract
Obesity is associated with low-grade chronic inflammation, and metabolic dysregulation. Evidence shows that chronic inflammation inhibits protective immunity mediated by CD4+ T cells. Additionally, obesity-induced inflammation affects prostate cancer progression. However, the effect of obesity on CD4+ T-cell- response to prostate cancer is not well understood. To investigate whether obesity induces changes in CD4+ T cell cytokine profile, cytokine expression was measured in splenic CD4+ T-cells from 10-week-old male C57Bl/6 mice exposed to conditioned media (CM) from macrophages grown in sera from obese subjects. Additionally, expression levels of key regulators of Epithelial-Mesenchymal Transition (EMT) were measure in prostate cancer epithelial cells exposed to conditioned media from obesity-modified T-cells. Cell migration and invasion was measured in prostate cancer epithelial cells exposed to CM from obesity-modified CD4+ T-cells. Obesity suppressed the expression of IFNγ and IL-2 in CD4+ T-cells but up-regulated the expression of IL-6. Prostate epithelial cancer cells exposed to conditioned media from obesity-modified T cell increased the expression of EMT markers and showed a higher invasive and migratory capacity.
Acknowledgments
The authors would like to thank Dr. Ramona S. Price for her feedback and input.
Author contribution statement
A.D., P.T., C.J., and L.D. conceived and planned the experiments. A.D. and P.T. carried out the experiments. G.C. contributed to sample preparation. All authors contributed to the interpretation of the results. A.D. took the lead in writing the manuscript. A.D., P.T., and G.G. contributed to revisions of the final version of the manuscript. L.D. supervised the project. All authors provided critical feedback and helped shape the research, analysis, and manuscript.
Disclosure statement
No competing financial interests exist. The authors have nothing to disclose.