TY - JOUR
T1 - Short-term stress enhances cellular immunity and increases early resistance to squamous cell carcinoma
AU - Dhabhar, Firdaus S.
AU - Saul, Alison N.
AU - Daugherty, Christine
AU - Holmes, Tyson H.
AU - Bouley, Donna M.
AU - Oberyszyn, Tatiana M.
N1 - Funding Information:
We thank Susie Jones for conducting immunohistochemistry, and Jean Tillie, Kanika Ghai, and Cynthia Walter, of the Dhabhar Laboratory for valuable assistance with these studies. Grant support: NIH RO1 CA107498 (F.S.D.).
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
KW - Cell-mediated immunity
KW - Cutaneous T-cell attracting chemokine (CTACK)
KW - Immune cells
KW - Psychological stress
KW - Skin cancer/tumor
KW - Th1-Th2 cytokines
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U2 - 10.1016/j.bbi.2009.09.004
DO - 10.1016/j.bbi.2009.09.004
M3 - Article
C2 - 19765644
AN - SCOPUS:72049133158
VL - 24
SP - 127
EP - 137
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
SN - 0889-1591
IS - 1
ER -