IMMUNOSUPPRESSIVE PARAMETERS IN SERUM OF OVARIAN CANCER
PATIENTS CHANGE DURING THE DISEASE COURSE
T. Baert1,2, J. Decoene1, A. Laenen3, A. Kasran4, T. Verschuere5, S. Seys4, I. Vergote1,2, A.
Coosemans1,2,
1
Department of Gynaecology and Obstetrics, UZ Leuven, Leuven, Belgium;
Department of Oncology, Laboratory of Gynaecologic Oncology, KU Leuven, Leuven,
Belgium;
3
Biostatistics and Statistical Bioinformatics Centre of Leuven, KU Leuven, Leuven, Belgium;
4
Department of Microbiology and Immunology, Laboratory of Clinical Immunology, KU
Leuven, Leuven, Belgium;
5
Department of Neuroscience, Laboratory of Experimental Neurosurgery, KU Leuven,
Leuven, Belgium;
2
Background: 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. We explored the immune changes in
ovarian cancer.
Material and methods: 135 serum samples from 80 ovarian cancer patients were collected at
diagnosis (n=50), after debulking surgery (n=15 (primary); n=19 (interval)) and after
chemotherapy (paclitaxel-carboplatin) (n=40). Serum (n=10) from an age-matched control
group was collected. To evaluate Treg, MDSC and TAM (specifically M2) in serum, we
analyzed their key metabolites: IL-4 (interleukin), IL-13, arginase, IL-10, VEGF (vascular
endothelial growth factor), CCL2 (chemokine (C-C) motif ligand 2) and TGF-β (transforming
growth factor). We also determined galectin-1, involved in angiogenesis and tumor-mediated
immune evasion. Metabolites were measured using Enzyme-Linked Immuno Sorbent Assay
(ELISA) or Cytometric Bead Array (CBA).
Results: Mean age was 61,9 years. 90% had serous ovarian carcinoma (65% FIGO stage III;
34% stage IV). We found significant lower levels of IL-10, VEGF, TGF-β and arginase and
higher levels of galectin-1 after chemotherapy compared to diagnosis. After debulking
surgery, a decrease in IL-10 was significant. Using multivariate analysis, including FIGO
stage, galectin-1 and CCL2 appeared independent prognostic factors for progression-free and
overall survival.
Conclusions: This study demonstrates changes in the immune system of ovarian cancer
patients due to chemotherapy and surgery. We defined two new prognostic markers. With
these results we gain insight in timing and determination of treatment, in order to further
modulate the immune system in a positive way.