Abstract A004: Comprehensive cytokine and chemokine evaluation in plasma samples of primary, non-metastatic high grade serous ovarian cancer patients to estimate outcome and platinum resistance

Abstract Background: Ovarian cancer (OC) still has the highest mortality rate of all gynecological malignancies, diagnosed mostly at advanced stages, resulting in a generally poor outcome. Radical tumor debulking, followed by platinum-based chemotherapy with/without bevacizumab and with/without PARP inhibitors is the standard of care in advanced OC. However, the majority of patients will ultimately relapse due to the development of platinum resistance. Efforts to apply immunotherapy has been less successful, however, immunologic processes play an important role in tumorigenesis and therapy response. Efforts to heat up the tumor microenvironment through cytokine modulation are being explored in many tumors, however, little is known about cytokine and chemokine expression in OC. In view of biomarker research to identify patients at high risk for relapse, we here determined cytokine and chemokine levels in blood samples of primary, non-metastatic, high grade serous (HGS) OC patients before and after therapy to estimate their value with regard to progression-free survival (PFS), overall survival (OS) and platinum resistance. Patients and Methods: Plasma samples of 29 HGSOC patients were collected both, prior (n=29) and following platinum-based chemotherapy (n=20) with/without bevacizumab. Cytokine and chemokine levels were quantified using the Olink Target 48 Cytokine panel (LuminoDX, San Diego, USA), which includes 45 immune-related proteins and requires only one μL of sample. Results were correlated between cytokine/chemokine levels and PFS and OS using the Cox proportional hazards model and Log-rank test as well as platinum resistance applying the student`s t-test. Results: The associations between cytokine and chemokine plasma levels and patient outcomes were first assessed using the Cox proportional hazards model. At baseline, enhanced levels of IL1B, IL6, IL17C, IL27 as well as VEGFA significantly correlated with a reduced PFS whereas enhanced levels of CCL4 significantly associated with a longer OS, using a significance threshold of p < 0.05. We observed an increase of IL13 over the course of treatment, which correlated with a shorter PFS. In contrast, increasing levels of IL17C, TNF and CCL2 over time were significantly related to a shorter OS whereas decreasing CCL4 (p=0.055) levels might qualify for indicating a longer OS. To visualize survival differences, Kaplan-Meier survival analyses with log-rank tests were performed for each analyte after dichotomizing patients into high and low expression groups based on median values. In addition, high IL6 levels and low CXCL12 and EGF levels were significantly associated with the development of platinum resistance. Conclusion: In this pilot study, we demonstrate the potential value of cytokine and chemokine plasma levels to better estimate PFS, OS as well as platinum resistance in HGSOC. These prognostic and predictive markers may be further developed into clinical assays to support patient management. Further patients are currently under evaluation to verify these observations. Citation Format: Yipeng Wang, Büsra Eser, Gordon Vansant, Stefanos Ioannis. Moukas, Paul Buderath, Rainer Kimmig, Fabinshy Thangarajah, Sabine Kasimir-Bauer. Comprehensive cytokine and chemokine evaluation in plasma samples of primary, non-metastatic high grade serous ovarian cancer patients to estimate outcome and platinum resistance [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr A004.