Hypothalamic brain-derived neurotrophic factor regulates lymphocyte immunity and cancer progression in environmental enrichment
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Date
2017-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
The Ohio State University
Abstract
Cancer is a heavily studied, multifactorial disease with an incidence of nearly 1.7 million in the U.S. alone. In a clinical study, a supportive social environment was shown to improve outcomes for breast cancer patients. Yet, animal model experiments have mainly focused on the negative effects of distress or social isolation on cancer outcomes. Our model of social enrichment, an enriched environment (EE), is a model of eustress, and we uniquely study the positive effects of the social environment on cancer outcomes. We have previously shown that EE exerts an anticancer effect. Here, we show that CD8 T-cells are required for this effect. Furthermore, we show a shift to CD8 T-cells in secondary lymphoid tissue that is mediated by a molecule in the hypothalamus, brain-derived neurotrophic factor. We also show a shift in thymocyte development toward CD8 T-cells in EE that is regulated by the same molecule. We have further studied the complex effect of EE on the adipose tissue microenvironment, specifically on natural-killer cells. Here, we show that adipose tissue-specific IL-15 overexpression results in increased NK cells in adipose tissue as well as increased NK cells at a nearby tumor and decreased mass of the nearby tumor. Finally, we extend the current knowledge of EE's anticancer effect to a blood cancer, acute myeloid leukemia, in which we see a substantial increase in progression-free survival but a modest, yet still significant, increase in overall survival. These results together show the complex connection between the environment, the nervous system, the immune system, and the cancer microenvironment in mice. The continual regulation of EE's anticancer effect by brain-derived neurotrophic factor suggests the possibility of manipulating a single gene in the brain for beneficial outcomes in certain cancers. Our model shows the importance of studying the positive effects of the environment on cancer outcomes as a model for human disease.
Description
Denman 2016 Honorable Mention
Keywords
environmental enrichment, T-cells, cancer, BDNF
Citation
Published version: Run Xiao, Stephen M. Bergin, Wei Huang, Andrew M. Slater, Xianglan Liu, Ryan T. Judd, En-Ju D. Lin, Kyle J. Widstrom, Steven D. Scoville, Jianhua Yu, Michael A. Caligiuri and Lei Cao, Environmental and Genetic Activation of Hypothalamic BDNF Modulates T-cell Immunity to Exert an Anticancer Phenotype, Cancer Immunology Research, Volume 4, Issue 6, 1 June 2016, Pages 488-497. https://doi.org/10.1158/2326-6066.CIR-15-0297