Abstract 2872: Site specific tumor microenvironments modulate the immune checkpoint inhibitors response in models of CT26 colon carcinoma

Abstract

Abstract Syngeneic models provide a robust platform to test new and cutting edge immune-oncology therapies. CT26 is a popular syngeneic colon carcinoma model that is known to respond to immune checkpoint inhibitors when engrafted into Balb/c mice as a subcutaneous flank tumor. The subcutaneous flank implant location provides a robust model, that is easy to set up, and allows for continuous measurement of the tumor growth by calipering. However, the location of tumor implant has been shown to impact tumor microenvironment and immune response for a number of cancer cell lines (Zhao 2017, Brand 2021, Oliver 2018). In addition to subcutaneous flank tumors, CT26 can be implanted to generate a lung metastasis or peritoneal metastasis model. We were interested to see if the lung metastasis or peritoneal metastasis CT26 model responded differently to immune checkpoint inhibition compared with the subcutaneous model and whether the different implant locations resulted in changes to the tumor infiltrating lymphocytes. CT26 cells were either injected intravenously to induce a lung metastasis model, intraperitoneally to produce a peritoneal metastasis model, or subcutaneously to generate a solid flank tumor model. Immune checkpoint inhibitor (ICI) therapy began on Day 5 following implant in each model, and tumor progression or survival provided the endpoint for analysis. In addition, tumor infiltrating leukocytes were assessed by flow cytometry to determine differences in the overall tumor microenvironment for each model. The response to both anti-PD-1 and anti-CTLA-4 monotherapies were strongest in the subcutaneous flank model, followed by moderate responses in the lung metastasis model, and no significant response to either ICI in the peritoneal metastasis model. This provides researchers with an opportunity to assess the ability of novel immune-oncology therapies to provoke an immunogenic response in models with identical antigenicity, but different tumor microenvironments based on the tumor location. Citation Format: Fei Zhao, Caitlin Thompson, Nicole Barnes, José Roques, Terrence Coleman, Tyler Rowe, Joseph Kolb, Chassidy Hall, Patrick Fadden. Site specific tumor microenvironments modulate the immune checkpoint inhibitors response in models of CT26 colon carcinoma [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 2872.