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Social Support, Psychological Distress, and Natural Killer Cell Activity in Ovarian Cancer

From the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Departments of Biostatistics, Psychology, Urology, and Microbiology, and the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA; Department of Gynecologic Oncology, University of Texas M.D. Anderson Comprehensive Cancer Center, Houston, TX; and Department of Obstetrics and Gynecology, Hartford Hospital, Hartford, CT

Address reprint requests to Susan Lutgendorf, PhD, Associate Professor, Departments of Psychology and Obstetrics and Gynecology, E11 Seashore Hall, University of Iowa, Iowa City, IA 52242; e-mail: susan-lutgendorf{at}uiowa.edu

PURPOSE: Psychosocial stress has been related to impaired immunity in cancer patients. However, the extent to which these relationships exist in immune cells in the tumor microenvironment in humans has not been explored. We examined relationships among distress, social support, and natural killer (NK) cell activity in ovarian cancer patients in peripheral-blood mononuclear cells (PBMC), ascitic fluid, and tumor-infiltrating lymphocytes (TIL).

PATIENTS AND METHODS: Patients awaiting surgery for a pelvic mass suspected of being ovarian cancer completed psychological questionnaires and gave a presurgical sample of peripheral blood. Samples of tumor and ascites were taken during surgery, lymphocytes were then isolated, and NK cytotoxicity and percentage were determined. The final sample, which was confirmed by surgical diagnosis, included 42 patients with epithelial ovarian cancer and 23 patients with benign masses.

RESULTS: Peripheral NK cell activity was significantly lower among ovarian cancer patients than in patients with benign masses. Among ovarian cancer patients, NK cytotoxicity in TIL was significantly lower than in PBMC or ascitic fluid. Social support was related to higher NK cytotoxicity in PBMC and TIL, adjusting for stage. Distress was related to lower NK cytotoxicity in TIL. A multivariate model indicated independent associations of both distress and social support with NK cell activity in TIL.

CONCLUSION: Psychosocial factors, such as social support and distress, are associated with changes in the cellular immune response, not only in peripheral blood, but also at the tumor level. These relationships were more robust in TIL. These findings support the presence of stress influences in the tumor microenvironment.

Supported in part by grant Nos. R21 CA88293 and RO1-CA1045-25 (S.K.L.) from the National Cancer Institute, Bethesda, MD.

Presented in part at a meeting entitled Exploring the Integration of Psychoneuroimmunology and Tumor Immunology in Cancer Control Research, Bethesda, MD, April 15-16, 2004; at the Academy of Behavioral Medicine Research, Jackson Hole, WY, June 10-13, 2004; at the 63rd Annual Meeting of the American Psychosomatic Society, Vancouver, British Columbia, Canada, March 2-5, 2005; and at the 31st Annual Meeting of the Society for Gynecologic Oncology Annual Meeting, Miami, March 19-23, 2005.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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