Chronic restraint stress impairs T-cell immunity and promotes tumor progression in mice.
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.
Frick
L R
LR
Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Cientificas y Técnicas, 1 Cátedra de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. lfrick@fmed.uba.ar
Arcos
M L Barreiro
ML
Rapanelli
M
M
Zappia
M P
MP
Brocco
M
M
Mongini
C
C
Genaro
A M
AM
Cremaschi
G A
GA
D000818:Animals; D001522:Behavior, Animal; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma