Rikki A Cannioto1, Lara E Sucheston-Campbell1, Shalaka Hampras2, Ellen L Goode3, Keith Knutson3, Roberta Ness4, Francesmary Modugno5, Paul Wallace6, J Brian Szender7, Paul Mayor7, Chi-Chen Hong1, Janine M Joseph1, Grace Friel1, Warren Davis1, Mary Nesline8, Kevin H Eng9, Robert P Edwards10, Bridget Kruszka1, Kristina Schmitt1, Kunle Odunsi7, Kirsten B Moysich1. 1. Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Buffalo, NY. 2. Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL. 3. Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, MN. 4. School of Public Health, The University of Texas, Houston, TX. 5. Department of Epidemiology and Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh and Women's Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA. 6. Department of Flow and Image Cytometry, Roswell Park Cancer Institute, Buffalo, NY. 7. Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, NY. 8. Center for Personalized Medicine, Roswell Park Cancer Institute, Buffalo, NY. 9. Department of Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY. 10. Department of Obstetrics, Gynecology & Reproductive Sciences and Ovarian Cancer Center of Excellence, University of Pittsburgh, Pittsburgh, PA.
Abstract
OBJECTIVE: There is a mounting body of evidence demonstrating higher percentages of regulatory T (Treg) cells in the peripheral blood of patients with cancer in comparison to healthy controls, but there is a paucity of epidemiological literature characterizing circulating Treg cells among patients with epithelial ovarian cancer (EOC). To investigate the role of peripheral Treg cells in ovarian neoplasms, we conducted a case-control study to characterize circulating concentrations of Treg cells among patients with EOC, women with benign ovarian conditions, and healthy controls without a history of cancer. MATERIALS AND METHODS: Participants were identified for inclusion due to their participation in the Data Bank and BioRepository program at Roswell Park Cancer Institute in Buffalo, NY. Patients included 71 women with a primary diagnosis of EOC and 195 women with a diagnosis of benign ovarian conditions. Controls included 101 age- and race-matched women without a history of cancer. Nonfasting, pretreatment peripheral blood levels of CD3+CD4+CD25+FOXP3+ Treg cells were measured using flow cytometric analyses and expressed as a percentage of total CD3+ cells and as a percentage of total CD3+CD4+ cells. RESULTS: Compared to healthy controls and women with benign ovarian conditions, patients with EOC had significantly higher frequency of Treg cells (P < 0.04). In multivariable logistic regression analyses using Treg frequency expressed as a percentage of CD+3 cells, we observed a significant positive association between Treg cell percentage and EOC risk, with each 1% increase associated with a 37% increased risk of EOC (odds ratio, 1.37; 95% confidence interval, 1.04-1.80). We observed a similar trend when Treg frequency was expressed as a percentage of CD3+CD+4 cells (odds ratio, 1.22; 95% confidence interval, 0.99-1.49). CONCLUSIONS: The current study provides support that peripheral Treg cell frequency is elevated in patients with EOC in comparison to women with benign ovarian conditions and healthy controls.
OBJECTIVE: There is a mounting body of evidence demonstrating higher percentages of regulatory T (Treg) cells in the peripheral blood of patients with cancer in comparison to healthy controls, but there is a paucity of epidemiological literature characterizing circulating Treg cells among patients with epithelial ovarian cancer (EOC). To investigate the role of peripheral Treg cells in ovarian neoplasms, we conducted a case-control study to characterize circulating concentrations of Treg cells among patients with EOC, women with benign ovarian conditions, and healthy controls without a history of cancer. MATERIALS AND METHODS:Participants were identified for inclusion due to their participation in the Data Bank and BioRepository program at Roswell Park Cancer Institute in Buffalo, NY. Patients included 71 women with a primary diagnosis of EOC and 195 women with a diagnosis of benign ovarian conditions. Controls included 101 age- and race-matched women without a history of cancer. Nonfasting, pretreatment peripheral blood levels of CD3+CD4+CD25+FOXP3+ Treg cells were measured using flow cytometric analyses and expressed as a percentage of total CD3+ cells and as a percentage of total CD3+CD4+ cells. RESULTS: Compared to healthy controls and women with benign ovarian conditions, patients with EOC had significantly higher frequency of Treg cells (P < 0.04). In multivariable logistic regression analyses using Treg frequency expressed as a percentage of CD+3 cells, we observed a significant positive association between Treg cell percentage and EOC risk, with each 1% increase associated with a 37% increased risk of EOC (odds ratio, 1.37; 95% confidence interval, 1.04-1.80). We observed a similar trend when Treg frequency was expressed as a percentage of CD3+CD+4 cells (odds ratio, 1.22; 95% confidence interval, 0.99-1.49). CONCLUSIONS: The current study provides support that peripheral Treg cell frequency is elevated in patients with EOC in comparison to women with benign ovarian conditions and healthy controls.
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