Restraint and social isolation stressors differentially regulate adaptive immunity and yumor angiogenesis in a breast cancer mouse model

Raluca A. Budiu, Anda M. Vlad, L. Nazario, C. Bathula, K.L. Cooper, Jessica Edmed, Premal H. Thaker, Julie Urban, Pawel Kalinski, Adrian V. Lee, Esther L. Elishaev, Thomas P. Conrads, Melanie Flint

Research output: Contribution to journalArticle

Abstract

The ability of stress to induce immune suppression is widely recognized, but the mechanisms underlying the effects of stress on the adaptive immune system during tumor progression are not completely understood. To study the effect of stress on the immune system in vivo, we used a preclinical immunocompetent mouse model bearing 4T1 mammary adenocarcinoma cells. Mice were randomized into 4 groups, including social isolation (SI), acute restraint stress (aRRS), chronic restraint stress (cRRS), or no stress (NS). We found that SI significantly decreased the number of tumor-bearing mice still alive at the end of protocol (28 days), compared to NS mice. Although we did not detect significant changes in primary tumor volume, we observed a significant increase in the endothelial marker CD31 in primary tumors of SI mice and in lung metastases in SI and RRS mice. Survival decline in SI mice was associated with significant decreases in splenic CD8 cells and in activated T cells. From a mechanistic standpoint, RRS increased expression of FOXP3, CXCL-10, and granzyme B in mouse tumors, and the effects were reversed by propranolol. Our data demonstrate that various forms of stress differentially impact adaptive immunity and tumor angiogenesis, and negatively impact survival.
Original languageEnglish
JournalCancer and clinical oncology
Volume6
Issue number1
DOIs
Publication statusPublished - 11 Nov 2016

Bibliographical note

Copyright for this article is retained by the author(s), with first publication rights granted to the journal. This is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).

Keywords

  • breast cancer
  • stress
  • social isolation
  • T cells
  • Tregs.

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    Budiu, R. A., Vlad, A. M., Nazario, L., Bathula, C., Cooper, K. L., Edmed, J., Thaker, P. H., Urban, J., Kalinski, P., Lee, A. V., Elishaev, E. L., Conrads, T. P., & Flint, M. (2016). Restraint and social isolation stressors differentially regulate adaptive immunity and yumor angiogenesis in a breast cancer mouse model. Cancer and clinical oncology, 6(1). https://doi.org/10.5539/cco.v6n1p12