Low plasma PD-L1 levels, early tumor onset and absence of peritoneal carcinomatosis improve prognosis of women with advanced high-grade serous ovarian cancer
Daniele Fanale,
Chiara Brando,
Lidia Rita Corsini,
Sofia Cutaia,
Mariano Catello Di Donna,
Ugo Randazzo,
Clarissa Filorizzo,
Chiara Lisanti,
Luigi Magrin,
Vittorio Gurrera,
Raffaella Romano,
Alessandra Dimino,
Tancredi Didier Bazan Russo,
Daniel Olive,
Salvatore Vieni,
Gianni Pantuso,
Antonio Giordano,
Vito Chiantera,
Antonio Russo,
Viviana Bazan,
Juan Lucio Iovanna
Affiliations
Daniele Fanale
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo
Chiara Brando
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo
Lidia Rita Corsini
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo
Sofia Cutaia
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo
Mariano Catello Di Donna
Department of Gynecologic Oncology, University of Palermo
Ugo Randazzo
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo
Clarissa Filorizzo
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo
Chiara Lisanti
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo
Luigi Magrin
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo
Vittorio Gurrera
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo
Raffaella Romano
Department of Gynecologic Oncology, University of Palermo
Alessandra Dimino
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo
Tancredi Didier Bazan Russo
Medicine and Surgery School, University of Palermo
Daniel Olive
Team Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes
Salvatore Vieni
Division of General and Oncological Surgery, Department of Surgical, Oncological and Oral Sciences, University of Palermo
Gianni Pantuso
Division of General and Oncological Surgery, Department of Surgical, Oncological and Oral Sciences, University of Palermo
Antonio Giordano
Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University
Vito Chiantera
Department of Gynecologic Oncology, University of Palermo
Antonio Russo
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo
Viviana Bazan
Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo
Juan Lucio Iovanna
Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique Et Technologique de Luminy
Abstract Background The most common subtype of ovarian cancer (OC) showing immunogenic potential is represented by the high-grade serous ovarian cancer (HGSOC), which is characterized by the presence of tumor-infiltrating immune cells able to modulate immune response. Because several studies showed a close correlation between OC patient’s clinical outcome and expression of programmed cell death protein-1 or its ligand (PD-1/PD-L1), the aim of our study was to investigate if plasma levels of immunomodulatory proteins may predict prognosis of advanced HGSOC women. Patients and methods Through specific ELISA tests, we analyzed plasma concentrations of PD-L1, PD-1, butyrophilin sub-family 3A/CD277 receptor (BTN3A1), pan-BTN3As, butyrophilin sub-family 2 member A1 (BTN2A1), and B- and T-lymphocyte attenuator (BTLA) in one hundred patients affected by advanced HGSOC, before surgery and therapy. The Kaplan–Meier method was used to generate the survival curves, while univariate and multivariate analysis were performed using Cox proportional hazard regression models. Results For each analyzed circulating biomarker, advanced HGSOC women were discriminated based on long (≥ 30 months) versus short progression-free survival (PFS 0.42 ng/mL), PD-1 (> 2.48 ng/mL), BTN3A1 (> 4.75 ng/mL), pan-BTN3As (> 13.06 ng/mL), BTN2A1 (> 5.59 ng/mL) and BTLA (> 2.78 ng/mL). Furthermore, a lower median PFS was associated with peritoneal carcinomatosis, age at diagnosis > 60 years or Body Mass Index (BMI) > 25. A multivariate analysis also suggested that plasma concentrations of PD-L1 ≤ 0.42 ng/mL (HR: 2.23; 95% CI: 1.34 to 3.73; p = 0.002), age at diagnosis ≤ 60 years (HR: 1.70; 95% CI: 1.07 to 2.70; p = 0.024) and absence of peritoneal carcinomatosis (HR: 1.87; 95% CI: 1.23 to 2.85; p = 0.003) were significant prognostic marker for a longer PFS in advanced HGSOC patients. Conclusions The identification of high-risk HGSOC women could be improved through determination of the plasma PD-L1, PD-1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels.
