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

Firdaus S. Dhabhar, Alison N. Saul, Christine Daugherty, Tyson H. Holmes, Donna M. Bouley, Tatiana M. Oberyszyn

Research output: Contribution to journalArticle

60 Scopus citations

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 (2.5 h) 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-γ 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.

Original languageEnglish (US)
Pages (from-to)127-137
Number of pages11
JournalBrain, Behavior, and Immunity
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Keywords

  • Cell-mediated immunity
  • Cutaneous T-cell attracting chemokine (CTACK)
  • Immune cells
  • Psychological stress
  • Skin cancer/tumor
  • Th1-Th2 cytokines

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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