Abstract 4156: Site specific tumor response to combination chemotherapy and immune checkpoint inhibitor in the syngeneic Pan02 pancreatic ductal adenocarcinoma model

Abstract

Abstract Syngeneic tumor models provide a platform to assess novel immune-oncology therapeutics in fully immuno-competent mice. A subcutaneous flank tumor implant provides a convenient and accessible location to monitor the tumor growth and response to therapy. However, the tumor microenvironment, and therefore, the responsiveness to immuno-oncology therapies, is greatly impacted by the location in which the tumor develops (Ho 2021, Oliver 2018). Given the potential of different immuno-suppressive features driven by the specific tumor location, we wanted to compare the tumor infiltrating leukocyte populations in the subcutaneous flank and orthotopic pancreatic Pan02 syngeneic models, as well as the response to standard of care therapies. Pan02 cells were either implanted orthotopically in the pancreas or subcutaneously in the flank and allowed to establish before dosing with either vehicle, oxaliplatin, anti-CTLA-4 or the combination of therapies. Established tumors from untreated orthotopic and flank models were sampled for flow cytometry to assess infiltration by a broad range of immune cell populations. Response to therapy was clearly dependent on tumor location with flank tumors being resistant to both monotherapy and combination therapy, while the orthotopic tumors responded modestly to monotherapy but displayed synergy with the combination therapy. The results suggest that for a given syngeneic tumor cell line with identical mutational load and antigenicity, we can generate unique tumor microenvironments dependent on implant location leading to different outcomes when testing novel immune-oncology therapies. These types of models can help define the context in which novel immune-oncology therapeutics can be expected to drive an effective immune response. Citation Format: Andrew Wong, Patrick Fadden, Cara Clouse, Patrick Wood, Marianna Brown-Augustine, Fei Zhao, Elliot Ser, Joseph Kolb, Chassidy Hall, Elizabeth Rainbolt. Site specific tumor response to combination chemotherapy and immune checkpoint inhibitor in the syngeneic Pan02 pancreatic ductal adenocarcinoma model. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4156.