Chronic restraint stress impairs T-cell immunity and promotes tumor progression in mice

Stress. 2009 Mar;12(2):134-43. doi: 10.1080/10253890802137437.

Abstract

Long-term exposure to stressful situations can affect the immune system. The T-cell response is an important component of anti-tumoral immunity. Hence, impairment of the immune function induced by a chronic stressor has been postulated to alter the immunosurveillance of tumors, thus leading to a worse neoplastic prognosis. Here, we show that chronic restraint stress affects T-cell mediated immunity in mice. This was evidenced by a decrease of mitogen-induced T-cell proliferation, a reduction in CD4(+)T lymphocyte number and a decrease of tumor necrosis factor-alpha (TNF-alpha) and Interferon-gamma (IFN-gamma) production in stressed mice. Additionally, mice subjected to chronic restraint stress displayed an enhancement of tumor growth in a syngeneic lymphoma model, i.e. an increase of tumor proliferation and a reduction of animal survival. Finally, stressed mice had a reduced specific cytotoxic response against these tumor cells. These results suggest that chronic exposure to stress promotes cancer establishment and subsequent progression, probably by depressing T-cell mediated immunity. The T-cell immunity impairment as well as the tumor progression enhancement emphasize the importance of the therapeutic management of stress to improve the prognosis of cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Female
  • Interferon-gamma / biosynthesis
  • Killer Cells, Natural / immunology
  • Lymphoma, T-Cell / immunology*
  • Lymphoma, T-Cell / pathology
  • Mice
  • Mice, Inbred BALB C
  • Restraint, Physical
  • Stress, Psychological / immunology*
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Tumor Necrosis Factor-alpha
  • Interferon-gamma