Short-term stress enhances cellular immunity and increases early resistance to squamous cell carcinoma.

Abstract

In contrast to chronic/long-term stress that suppresses/dysregulates immune function, an acute/short-term fight-or-flight stress response experienced during immune activation can enhance innate and adaptive immunity. Moderate ultraviolet-B (UV) exposure provides a non-invasive system for studying the naturalistic emergence, progression and regression of squamous cell carcinoma (SCC). Because SCC is an immunoresponsive cancer, we hypothesized that short-term stress experienced before UV exposure would enhance protective immunity and increase resistance to SCC. Control and short-term stress groups were treated identically except that the short-term stress group was restrained (2.5h) before each of nine UV-exposure sessions (minimum erythemal dose, 3-times/week) during weeks 4-6 of the 10-week UV exposure protocol. Tumors were measured weekly, and tissue collected at weeks 7, 20, and 32. Chemokine and cytokine gene expression was quantified by real-time PCR, and CD4+ and CD8+ T cells by flow cytometry and immunohistochemistry. Compared to controls, the short-term stress group showed greater cutaneous T-cell attracting chemokine (CTACK)/CCL27, RANTES, IL-12, and IFN-gamma gene expression at weeks 7, 20, and 32, higher skin infiltrating T cell numbers (weeks 7 and 20), lower tumor incidence (weeks 11-20) and fewer tumors (weeks 11-26). These results suggest that activation of short-term stress physiology increased chemokine expression and T cell trafficking and/or function during/following UV exposure, and enhanced Type 1 cytokine-driven cell-mediated immunity that is crucial for resistance to SCC. Therefore, the physiological fight-or-flight stress response and its adjuvant-like immuno-enhancing effects, may provide a novel and important mechanism for enhancing immune system mediated tumor-detection/elimination that merits further investigation.

• Authors: Firdaus S Dhabhar, Alison N Saul, Christine Daugherty, Tyson H Holmes, Donna M Bouley, Tatiana M Oberyszyn
• Journal: Brain, behavior, and immunity (Brain Behav Immun) Vol. 24 Issue 1 Pg. 127-37 (Jan 2010) ISSN: 1090-2139 [Electronic] Netherlands
• PMID: 19765644 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Chemokines
• Cytokines

Topics

• Animals
• Behavior, Animal (physiology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Carcinoma, Squamous Cell (immunology)
• Cell Count
• Chemokines (biosynthesis)
• Cytokines (biosynthesis)
• Female
• Gene Expression
• Immunity, Cellular (immunology)
• Immunohistochemistry
• Kaplan-Meier Estimate
• Mice
• Stress, Psychological (immunology, psychology)
• Survival
• Ultraviolet Rays