title: Immunosuppressive parameters in serum of ovarian cancer patients change during the disease course.
abstract: Neoplastic cells can escape immune control leading to cancer growth. Regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) are crucial in immune escape. TAM are divided based on their immune profile, M1 are immunostimulatory while M2 are immunosuppressive. Research so far has mainly focused on the intratumoral behavior of these cells. This study, on the other hand, explored the systemic changes of the key metabolites [IL-4 (interleukin), IL-13, arginase, IL-10, VEGF-A (vascular endothelial growth factor), CCL-2 (chemokine (C-C) motif ligand 2) and TGF-β (transforming growth factor)] linked to Treg, MDSC and TAM during the course of the disease in ovarian and fallopian tube cancer patients. Serum samples were therefore analyzed at diagnosis, after (interval)-debulking surgery and after chemotherapy (paclitaxel-carboplatin). We also determined galectin-1 (gal-1), involved in angiogenesis and tumor-mediated immune evasion. We found significantly lower levels of IL-10, VEGF-A, TGF-β and arginase and higher levels of gal-1 after chemotherapy compared to diagnosis. After debulking surgery, a decrease in IL-10 was significant. Gal-1 and CCL-2 appeared independent prognostic factors for progression-free and overall survival (OS) (multivariate analysis). These results will help us in the decision making of future therapies in order to further modulate the immune system in a positive way.
authors.affiliation: Department of Gynecology and Obstetrics, UZ Leuven, Leuven, Belgium; Department of Oncology, Laboratory of Gynecologic Oncology, ImmunOvar Research Group, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Coosemans
authors.affiliation: Department of Gynecology and Obstetrics, UZ Leuven , Leuven, Belgium.
authors.forename: Judit
authors.initials: J
authors.lastname: Decoene
authors.affiliation: Department of Gynecology and Obstetrics, UZ Leuven, Leuven, Belgium; Department of Oncology, Laboratory of Gynecologic Oncology, ImmunOvar Research Group, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
authors.forename: Thaïs
authors.initials: T
authors.lastname: Baert
authors.affiliation: Biostatistics and Statistical Bioinformatics Center of Leuven, KU Leuven , Leuven, Belgium.
authors.forename: Annouschka
authors.initials: A
authors.lastname: Laenen
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Clinical Immunology, KU Leuven , Leuven, Belgium.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Kasran
authors.affiliation: Department of Neuroscience, Laboratory of Experimental Neurosurgery, KU Leuven , Leuven, Belgium.
authors.forename: Tina
authors.initials: T
authors.lastname: Verschuere
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Clinical Immunology, KU Leuven , Leuven, Belgium.
authors.forename: Sven
authors.initials: S
authors.lastname: Seys
authors.affiliation: Department of Gynecology and Obstetrics, UZ Leuven, Leuven, Belgium; Department of Oncology, Laboratory of Gynecologic Oncology, ImmunOvar Research Group, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
keywords: Arginase; CCL-2; VEGF; debulking; galectin-1; immunosuppression; ovarian cancer; paclitaxel–carboplatin