Immune focused interventions remain a high priority for many drug discovery efforts, spurred on by the success of immune checkpoint therapies such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 inhibitory antibodies. Preclinical efficacy assessments of novel immune-oncology therapies requires a functional immune system which limits the usefulness of traditional xenograft models and drive the use of humanized (human immune cell engrafted animals) and syngeneic model systems. Syngeneic mouse tumors are popular model systems in which to evaluate these novel therapies due the presence of fully intact mouse immune system and ease of accessibility. The MC38 mouse colon cancer model is popular for efficacy assessment studies due to its responsiveness to typical immune checkpoint inhibitors. We endeavored to characterize the immune response to checkpoint inhibitors in MC38 tumors using flow cytometry, gene expression analysis, and immunohistochemistry (IHC). Gene expression analysis provided a signature of gene changes that correlate to immune driven changes in tumor growth and may be used in preclinical pharmacodynamics studies as evidence of mode of action for other novel immune-oncology therapies. In addition, gene overrepresentation analysis highlighted the presence and involvement of B cell populations in the MC38 tumor environment which was supported by IHC data that show distinctive B cell staining in what resemble tumor associated tertiary lymph structures. These finding suggests that MC38 may provide a good model system for evaluating therapies that can modulate or impact tumor infiltrating B cell populations.

Citation Format: Patrick Fadden, Thi Bui, David Hurtado, Kelli Davis, Ian Belle, Kathrine Krontz, Jacob Hauser, Na Li, Kyle Takayama, Cristina Sokolowski, Edgar Wood. Characterization of the immune checkpoint inhibitor response in the MC38 murine colon cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-060.