TY - JOUR
T1 - Depressed and anxious mood and T-cell cytokine expressing populations in ovarian cancer patients
AU - Lutgendorf, Susan K.
AU - Lamkin, Donald M.
AU - DeGeest, Koen
AU - Anderson, Barrie
AU - Dao, Minh
AU - McGinn, Stephanie
AU - Zimmerman, Bridget
AU - Maiseri, Heena
AU - Sood, Anil K.
AU - Lubaroff, David M.
N1 - Funding Information:
This research was funded in part by Grants #R21CA88293 and #RO1CA104825 to Susan Lutgendorf from the National Cancer Institute. We thank Andrew Misfeldt, Joshua Lukenbill, Hannah Chang, Daniel Pederson, and Elizabeth King for assistance with immunologic assays, Joel Sorosky, David Bender, and Michael Goodheart for assistance with patient recruitment, and Anna Hoffman for assistance in study administration.
PY - 2008/8
Y1 - 2008/8
N2 - The adaptive immune response of ovarian cancer patients has been linked to survival, and is known to be impaired in the tumor microenvironment. Little is known about relationships between biobehavioral factors such as depressed mood and anxiety and the adaptive immune response in ovarian cancer. Thirty-seven patients with epithelial ovarian cancer and 14 patients with benign ovarian neoplasms completed psychosocial questionnaires pre-surgery. Lymphocytes from peripheral blood, tumor, and ascites (fluid around the tumor), were obtained on the day of surgery. Expression of the Type-1 cytokine interferon-gamma (IFNγ), and the Type-2 cytokine interleukin-4 (IL-4) by T-helper (CD4+) and T-cytotoxic (CD8+) cells was measured under autologous tumor-stimulated, polyclonally-stimulated, or unstimulated conditions. Links with mood were examined. Among cancer patients, marked elevations in unstimulated and tumor-stimulated Type-2 responses were seen, particularly in ascites and tumor-infiltrating lymphocytes (P values < 0.01). With polyclonal stimulation, lymphocytes from all compartments expressed elevated Type-1 cytokines (P values < 0.014). Depressed and anxious mood were both associated with significantly lower ratios of polyclonally-stimulated CD4+ cells producing IFNγ (TH1 cells) vs. IL-4 (TH2 cells) in all compartments (depressed mood: P = 0.012; anxiety: P = 0.038) and depressed mood was also related to lower ratios of polyclonally-stimulated CD8+ cells producing IFNγ (TC1) vs. IL-4 (TC2) (P = 0.035). Although effects of polyclonal stimulation should be generalized with caution to the in vivo immune response, findings suggest that depressed and anxious mood are associated with greater impairment of adaptive immunity in peripheral blood and in the tumor microenvironment among ovarian cancer patients.
AB - The adaptive immune response of ovarian cancer patients has been linked to survival, and is known to be impaired in the tumor microenvironment. Little is known about relationships between biobehavioral factors such as depressed mood and anxiety and the adaptive immune response in ovarian cancer. Thirty-seven patients with epithelial ovarian cancer and 14 patients with benign ovarian neoplasms completed psychosocial questionnaires pre-surgery. Lymphocytes from peripheral blood, tumor, and ascites (fluid around the tumor), were obtained on the day of surgery. Expression of the Type-1 cytokine interferon-gamma (IFNγ), and the Type-2 cytokine interleukin-4 (IL-4) by T-helper (CD4+) and T-cytotoxic (CD8+) cells was measured under autologous tumor-stimulated, polyclonally-stimulated, or unstimulated conditions. Links with mood were examined. Among cancer patients, marked elevations in unstimulated and tumor-stimulated Type-2 responses were seen, particularly in ascites and tumor-infiltrating lymphocytes (P values < 0.01). With polyclonal stimulation, lymphocytes from all compartments expressed elevated Type-1 cytokines (P values < 0.014). Depressed and anxious mood were both associated with significantly lower ratios of polyclonally-stimulated CD4+ cells producing IFNγ (TH1 cells) vs. IL-4 (TH2 cells) in all compartments (depressed mood: P = 0.012; anxiety: P = 0.038) and depressed mood was also related to lower ratios of polyclonally-stimulated CD8+ cells producing IFNγ (TC1) vs. IL-4 (TC2) (P = 0.035). Although effects of polyclonal stimulation should be generalized with caution to the in vivo immune response, findings suggest that depressed and anxious mood are associated with greater impairment of adaptive immunity in peripheral blood and in the tumor microenvironment among ovarian cancer patients.
KW - Anxiety
KW - Cytokines
KW - Depressed mood
KW - Distress
KW - Ovarian cancer
KW - Psychoneuroimmunology
KW - T-cell response
KW - Tumor microenvironment
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U2 - 10.1016/j.bbi.2007.12.012
DO - 10.1016/j.bbi.2007.12.012
M3 - Article
C2 - 18276105
AN - SCOPUS:46049102610
SN - 0889-1591
VL - 22
SP - 890
EP - 900
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
IS - 6
ER -