Abstract 2770: Evaluation of tumor growth and baseline leukocyte infiltration in Charles River C57BL/6 and Balb/c mice engrafted with MC38, B16F10, RENCA and EMT6 cells

Abstract

Abstract Background: In vivo syngeneic models continue to be an important tool in cancer biology research. Charles River C57BL/6 and Balb/c mice, two frequently used inbred strains, can be implanted with different murine tumor cell lines. One aspect of syngeneic model development is to characterize the extent and composition of infiltrating leukocytes (TIL) of tumor-bearing mice. The ability to analyze TILs is a relevant factor in preclinical model selection for studying immunomodulatory responses. Study Details: We evaluated growth rates and basal infiltrates in syngeneic models of solid mouse tumors. In four separate studies 7-week-old Charles River mice were implanted subcutaneously on the flank with either MC38 or B16F10 cells (C57BL/6) or with either RENCA or EMT6 cells (Balb/c), respectively. Mice were treated with isotype control IgG1 antibody (BioXcell clone MOPC-21) when tumors reached sizes of ~50-100 mm3. Surviving mice were euthanized when tumor burden reached or exceeded 2000 mm3 in line with internal IACUC guidelines. Spleen and tumors were then processed into single cell suspensions for immunophenotyping by multicolor acoustic-assisted flow cytometry. Results: Growth kinetics of all four tumor cell lines, MC38, B16F10, RENCA and EMT6, were monitored throughout each study. At study termination murine leukocyte infiltration was found in all models. These TILs were immune profiled to determine the frequencies and composition of murine immune cells in the lymphoid and myeloid compartments. Phenotyping data confirmed the presence of viable CD45+ cells with total T-cells (CD3+), T-cell subsets (CD4+, CD8+ and Treg) and myeloid populations (CD11b+) including M1 and M2 TAMs as well as CD11c+ cells. M1/M2 TAM, CD8/Treg and CD4/CD8 ratios were also calculated, and tumor models were assessed based on their baseline TIL composition. Conclusions: Four different allograft models of solid mouse tumors could be established using Charles River C57BL/6 and Balb/c mice. Their basal immune microenvironments could be characterized and therefore can be useful as pharmacodynamic readouts in efficacy studies of potential anti-cancer therapeutics. Citation Format: Christoph S. Eberle, Jenny Rowe, Ann Fiore, Robert Mihalek, Stephen Festin. Evaluation of tumor growth and baseline leukocyte infiltration in Charles River C57BL/6 and Balb/c mice engrafted with MC38, B16F10, RENCA and EMT6 cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2770.