Chronic cisplatin treatment led to upregulation of cGAS and STING proteins in 2F8cis compared to parental 2F8 cells, while acute exposure to cisplatin further increases cGAS and STING levels in both 2F8 and 2F8cis cells. One of the pathways activated by cisplatin treatment is the cGAS/STING pathway. Cisplatin also upregulates PD-L1 expression in vitro and in vivo, demonstrating a dual, paradoxical immune modulatory effect and supporting the rationale for combination with immune checkpoint blockade. Acute and chronic exposure to cisplatin enhances tumor immunogenicity by increasing calreticulin, MHC class I, antigen presentation and T-cell infiltration. The 2F8 and its platinum-resistant derivative 2F8cis model, display distinct inflammatory profiles and chemotherapy sensitivities, and mirror the primary and recurrent human disease, respectively. Here, we evaluated the impact of cisplatin on tumor immunogenicity and its in vivo roles when used alone or in combination with anti-PD-L1, in two novel murine ovarian cancer cell models. To increase their clinical efficacy, checkpoint inhibitors are now being tested in clinical trials in combination with chemotherapy. New therapeutic approaches using immunotherapy via immune checkpoint blockade, which have demonstrated clinical efficacy in other tumor types, have been less promising in ovarian cancer. backbone of ovarian cancer treatment is platinum-based chemotherapy and aggressive surgical debulking. 10 Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 9 Magee Womens Research Institute, Pittsburgh, Pennsylvania, USA.1 Magee Womens Research Institute, Pittsburgh, Pennsylvania, USA. 8 Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.7 Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.6 Department of Epidemiology and Biostatistics, University of Maryland School of Public Health, College Park, Pittsburgh, MD, USA.5 Department of Biostatistics, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA, USA.4 Central South University Xiangya School of Medicine, Changsha, Hunan, People's Republic of China.3 Magee Womens Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA.2 Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.1 Magee Womens Research Institute, Pittsburgh, Pennsylvania, USA.

S Vlad Models