Abstract 5637: Investigating tumor intrinsic PD-1/PD-L1 signaling in canine osteosarcoma cell lines as a spontaneous model for human disease

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Abstract There is limited advancement in osteosarcoma therapy in humans. Interestingly, dogs spontaneously develop very similar disease at higher frequency, making canines a perfect model to study OS. Recent introduction of immune checkpoint blockade has revolutionized cancer therapy. Despite huge success, immunotherapy is still not effective in some group of patients or cancer types, and largely ineffective in sarcomas. Until recently, immune-checkpoint therapy was considered to block the interaction between PD-L1 expressed by cancer cells and PD-1 receptor localized on T-cells. Surprisingly, latest studies showed that cancer cells not only express PD-L1 but also PD-1 what is associated with increased growth, proliferation and survival via mTOR pathway signalling. Our group use canine osteosarcoma cell lines to investigate the role of PD-1/PD-L1 intrinsic signalling in disease pathogenesis. Flow cytometry confirmed PD-1 spontaneous expression on many OS cell lines, which ranged between 0.26% and 33.3%. Phenotypic changes were observed in PD-1/PD-L1 transfected over-expressing cells (OE). Strikingly, when grown in 3D culture, over-expressing cells shown accelerated growth and formation of spheres. Upregulation of pS6RP in PD-1 and PD-L1 OE cell lines indicated increased mTOR pathway signaling as demonstrated by Western Blot analysis. To confirm the impact of PD-1 antibody on canine cells, cell viability assay was performed after PD-1 blocking antibody treatment. Interestingly although in many of the cell lines, the addition of the antibody did not alter the growth, in one cell line the growth accelerated, while in another the proliferation decreased. Our data implies that the PD-1/PD-L1 intrinsic signalling may be important in canine osteosarcoma and targeting it could help enhance the therapeutic effect in both dogs and humans. Citation Format: Dziubek Katarzyna, Mikolaj Kocikowski, Borek Vojtesek, David Argyle, Malgorzata Lisowska, Ted Hupp, Maciej Parys. Investigating tumor intrinsic PD-1/PD-L1 signaling in canine osteosarcoma cell lines as a spontaneous model for human disease [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5637.