Ovarian cancer is the most lethal gynecological malignancy, frequently diagnosed at an advanced stage and with poor long-term survival rates. At first relapse, approximately 25% of patients have platinum-resistant/refractory ovarian cancer and almost all patients with recurrent disease ultimately develop platinum resistance. Platinum resistance, defined as disease relapse occurring within 6 months after the last platinum-based adjuvant chemotherapy cycle, is associated with worse PFS and OS, especially in High Grade Serous Ovarian cancer (HGSOC) patients.
Optimal management of recurrent platinum-resistant/refractory ovarian cancer remains an area of uncertainty.
The advent of the immune-oncology Era forced researchers and oncologist to take into account the immunological profile of the host and its modulation during the course of anticancer treatments. This new clinical approach shed a light on the urgent need of better understanding how the circulating immune system behaves during the course of the platinum-resistant disease and whether the analysis of platinum-resistant compared to platinum-sensitive tumor is able to predict, through an immunological signature, the development of platinum resistance.
For this reason, aim of the present study is to evaluate, in 60 primary platinum-resistant HGSOC serological samples derived from peripheral blood collection, a panel of 14 circulating immune-related proteins expression, thus tracing a circulating immunological signature possibly able to predict patients' treatment response and survival outcome. The same signature will be tested on a control cohort of primary platinum-sensitive HGSOC.
Half of samples will be delivered from Tumor Bank Ovarian Cancer Laboratory (TOC Lab), at Department of Gynecology, Charité Universitatsmedizin Berlin, Berlin, Germany.
Serological samples will be tested for presence and quantity of the 14 immune-related proteins by a selection panel from ProcartaPlex assay (Thermo Fisher).
Ovarian cancer(OC) is currently the most lethal malignancy among gynecological neoplasms (1). It has a large tumor burden which has been shown to elicit a strong immune response polarized towards immunesuppression (2).In both neoplastic tissue and in peripheral blood, regulatory CD3+FoxP3+Tcells(Tregs) negatively influence response to therapies and patients' prognosis(3).The Tcell immunoinfiltrate can be rescued from exhaustion or anergy for a potent immune activation that has the potential to induce a clinical response in advanced or metastatic tumors (4).
In ovarian cancer, the high expression of immunosuppressive molecules and the recruitment of regulatory T cells (Treg) are the
mechanisms of immune evasion. The blockade of PD-1 and CTLA-4 has been shown to restore antitumor activity of dysfunctional T cells and to limit activity of Tregs (8-10). Optimal management of recurrent platinum-resistant/refractory ovarian cancer remains an area of uncertainty. This subgroup of patients constitutes, indeed, a heterogeneous spectrum of disease with a low response rate to therapy (10%-25%), generally of short duration.
In this context there is a urgent need of better understanding how the circulating immune system behaves during the course of the HGS platinum-resistant disease and whether the analysis of primary compared to recurrent tumor is able to predict, through an immunological signature, the development of platinum resistance. The present project, thanks to the TOC Network collaboration and to its unique and precious population of primary platinum-resistant and platinum-sensitive HGSOC ovarian cancer patients' serological samples, will be able to assess if there's a role exerted by the immune-related ovarian cancer circulating proteins in predicting OC patients' platinum-response, thus being able to tailor patients' treatment before relapse occurrence and possibly delay disease recurrence (in order to identify the biological basis to potentially switch platinum-resistance into platinum-sensitive disease).