Immune checkpoints as potential theragnostic biomarkers for epithelial ovarian cancer

• Published in: The International journal of biological markers 2023-12, Vol.38 (3-4), p.203-213
• Main Authors: Habel, Azza, Weili, Xu, Hadj Ahmed, Mariem, Stayoussef, Mouna, Bouaziz, Hanen, Ayadi, Mouna, Mezlini, Amel, Larbi, Anis, Yaacoubi-Loueslati, Basma
• Format: Article
• Language: English
• Subjects: B7-H1 Antigen - metabolism; Biomarkers; Biomarkers, Tumor; BTLA protein; Cancer immunotherapy; Carcinoma, Ovarian Epithelial; CD223 antigen; CD28 antigen; CD40 antigen; CD80 antigen; Chemotherapy; CTLA-4 protein; Female; Hepatitis A Virus Cellular Receptor 2 - therapeutic use; Humans; Immune checkpoint; Microenvironments; Ovarian cancer; Ovarian Neoplasms - pathology; Paclitaxel; PD-1 protein; PD-L1 protein; Programmed Cell Death 1 Receptor - metabolism; Serum levels; TLR2 protein; Toll-Like Receptor 2; Toll-like receptors; Tumor Microenvironment
• ISSN: 0393-6155; 1724-6008
• DOI: 10.1177/03936155231186163

Background Epithelial ovarian cancer (EOC) is the leading cause of death associated with gynecologic tumors. EOC is asymptomatic in early stages, so most patients are not diagnosed until late stages, highlighting the need to develop new diagnostic biomarkers. Mediators of the tumoral microenvironment may influence EOC progression and resistance to treatment. Aim To analyze immune checkpoints to evaluate them as theranostic biomarkers for EOC. Patients and methods Serum levels of 16 immune checkpoints were determined in EOC patients and healthy controls using the MILLIPLEX MAP® Human Immuno-Oncology Checkpoint Protein Magnetic Bead Panel. Results Seven receptors: BTLA, CD40, CD80/B7-1, GITRL, LAG-3, TIM-3, TLR-2 are differentially expressed between EOC and healthy controls. Serum levels of immune checkpoints in EOC patients are positively significantly correlated with levels of their ligands, with a higher significant correlation between CD80 and CTLA4 than between CD28 and CD80. Four receptors, CD40, HVEM, PD-1, and PD-L1, are positively associated with the development of resistance to Taxol-platinum-based chemotherapy. All of them have an acceptable area under the curve (>0.7). Conclusion This study has yielded a first panel of seven immune checkpoints (BTLA, CD40, CD80/B7-1, GITRL, LAG-3, TIM-3, TLR-2) associated with a higher risk of EOC and a second panel of four immune checkpoints (CD40, HVEM, PD-1, PD-L1) that may help physicians to identify EOC patients who are at high risk of developing resistance to EOC chemotherapy.