Johanna M Gostner1, Eva Obermayr2, Ioana E Braicu3, Nicole Concin4, Sven Mahner5, Adriaan Vanderstichele6, Jalid Sehouli3, Ignace Vergote6, Dietmar Fuchs7, Robert Zeillinger8. 1. Division of Medical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria. 2. Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center - Gynecologic Cancer Unit, Medical University of Vienna, Vienna, Austria. 3. Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Department of Gynecology, European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Berlin, Germany. 4. Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria. 5. Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 6. Division of Gynecological Oncology, Department of Obstetrics and Gynecology, Leuven Cancer Institute, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium. 7. Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria. 8. Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center - Gynecologic Cancer Unit, Medical University of Vienna, Vienna, Austria. Electronic address: robert.zeillinger@meduniwien.ac.at.
Abstract
OBJECTIVE: Circulating tumor cells (CTCs) may represent a chronic stimulus for the immune system. In the present study we investigated the potential association of CTCs, the immune activation marker neopterin, and the ratio of kynurenine to tryptophan (Kyn/Trp) as a measure for tryptophan breakdown. METHODS: Neopterin, tryptophan and kynurenine levels were measured in plasma samples from patients with benign gynecological diseases (n=65) and with primary advanced epithelial ovarian cancer (EOC) at diagnosis (n=216) and six months after adjuvant platinum-based chemotherapy (n=45) by an enzyme-linked immunosorbent assay and high performance liquid chromatography. The presence of CTCs had been assessed in a previous study by qPCR-based analysis of CTC-related transcripts in the blood. The respective plasma levels in EOC and benign samples were compared using a two-tailed Chi2 or Fisher's exact test. The associations of the analytes and Kyn/Trp with clinicopathological parameters, platinum-sensitivity, and the presence of CTC-related transcripts were assessed using a two-sided t-test. Associations with patient outcome were evaluated using Cox regression analysis. RESULTS: In EOC, elevated Kyn/Trp and neopterin levels were associated with advanced disease, peritoneal carcinomatosis, ascites, sub-optimal debulking, poor response to therapy and worse outcome. Likewise, neopterin and Kyn/Trp were elevated in CTC-positive patients, both at diagnosis and at follow-up in platinum-sensitive disease. CONCLUSIONS: We observed concomitant alterations of CTCs and immune system related biomarkers suggesting that immune responses along with increase of neopterin and Kyn/Trp concentrations are not necessarily only located at the site of the tumor, but may also go on in the circulation.
OBJECTIVE: Circulating tumor cells (CTCs) may represent a chronic stimulus for the immune system. In the present study we investigated the potential association of CTCs, the immune activation marker neopterin, and the ratio of kynurenine to tryptophan (Kyn/Trp) as a measure for tryptophan breakdown. METHODS:Neopterin, tryptophan and kynurenine levels were measured in plasma samples from patients with benign gynecological diseases (n=65) and with primary advanced epithelial ovarian cancer (EOC) at diagnosis (n=216) and six months after adjuvant platinum-based chemotherapy (n=45) by an enzyme-linked immunosorbent assay and high performance liquid chromatography. The presence of CTCs had been assessed in a previous study by qPCR-based analysis of CTC-related transcripts in the blood. The respective plasma levels in EOC and benign samples were compared using a two-tailed Chi2 or Fisher's exact test. The associations of the analytes and Kyn/Trp with clinicopathological parameters, platinum-sensitivity, and the presence of CTC-related transcripts were assessed using a two-sided t-test. Associations with patient outcome were evaluated using Cox regression analysis. RESULTS: In EOC, elevated Kyn/Trp and neopterin levels were associated with advanced disease, peritoneal carcinomatosis, ascites, sub-optimal debulking, poor response to therapy and worse outcome. Likewise, neopterin and Kyn/Trp were elevated in CTC-positive patients, both at diagnosis and at follow-up in platinum-sensitive disease. CONCLUSIONS: We observed concomitant alterations of CTCs and immune system related biomarkers suggesting that immune responses along with increase of neopterin and Kyn/Trp concentrations are not necessarily only located at the site of the tumor, but may also go on in the circulation.
Authors: Eva Obermayr; Elena Ioana Braicu; Stephan Polterauer; Liselore Loverix; Nicole Concin; Linn Woelber; Sven Mahner; Jalid Sehouli; Toon Van Gorp; Ignace Vergote; Robert Zeillinger; Stefanie Aust Journal: Cancers (Basel) Date: 2021-11-23 Impact factor: 6.639
Authors: Lukas Lanser; Patricia Kink; Eva Maria Egger; Wolfgang Willenbacher; Dietmar Fuchs; Guenter Weiss; Katharina Kurz Journal: Front Immunol Date: 2020-02-21 Impact factor: 7.561