Abstract LB-115: Tumor intrinsic PD-1/PD-L1 signalling induces mesenchymal to epithelial transition in canine osteosarcoma cells

Osteosarcoma (OS) is the most common primary tumor of the bone in both humans and dogs. The dog, with its spontaneously occurring OS, shared pathogenic pathways and active immune system is one of the best models for studying novel immunotherapeutic approaches to human OS. Checkpoint blockade using antibodies against PD-1 has revolutionized the current approach to treatment of melanoma and other cancers. Recent reports have also shown that tumor intrinsic signalling plays a potential role in the success of PD-1 blockade in melanoma although studies in OS have not been published to date. PD-1/PD-L1 signalling has been reported to have role in epithelial to mesenchymal transition. In this study, we wanted to characterize intrinsic PD-1 signalling in canine osteosarcoma. We have created a canine specific PD-1 monoclonal antibody and we identified that PD-1 is intrinsically expressed in the cell line tested- OSA31. To further characterize the effects of PD-1 expression in this cell line we cloned canine PD-1 into a pcDNA 3.1 expression vector and transfected the cell line. Transfection of the cell line with PD-1 resulted in phenotypic changes characteristic for mesenchymal to epithelial transition. Interestingly overexpression of PD-1 as well as blockade of this receptor using the created antibody, resulted in decrease in cellular proliferation. To our knowledge this is the first report to identify role of PD-1 in mesenchymal to epithelial transition. These findings also suggest that PD-1 may be a promising therapeutic target in canine OS and warrant future clinical trials. Citation Format: Maciej Parys, Marta Nekulová, Bořivoj Vojtěšek, Jakub Faktor, Ana Lima, Theodore Hupp. Tumor intrinsic PD-1/PD-L1 signalling induces mesenchymal to epithelial transition in canine osteosarcoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-115.