Abstract 6025: Baseline cytokine profiling in naïve and tumor-bearing Balb/c and C57BL/6 Charles River mice

Abstract

Abstract Background: Syngeneic studies are still the backbone of oncology research. These rely on immunocompetent mice to model anti-cancer immune responses elicited by experimental treatments. Cytokines mediate these responses through cell signaling, which contributes to an immunosuppressive milieu in the tumor microenvironment. Determining the secretion patterns of these protein modulators can help understand pathogenesis, disease progression and resistance to targeted therapies. To evaluate biological effects of potential interventions, we compared systemic cytokine activities in naïve and untreated tumor-bearing Balb/c and C57BL/6 mice. Study Details: Charles River wild type Balb/c (n=9) and C57BL/6 (n=10) mice were used for all experiments. CT26 and B16.F10 tumor cell lines for inoculations were purchased from ATCC (Manassas, VA). Serum samples were collected from colon carcinoma (Balb/c) and melanoma (C57BL/6) bearing mice as well as tumor-free animals. For rapid multiplex measurements on the Meso Scale Discovery platform the V-PLEX Proinflammatory Panel 1 Mouse Kit was used (cat no. K15048D-1). IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, KC/GRO, IL-10, IL-12p70, and TNF-α were detected simultaneously by electrochemiluminescence within the manufacturer’s specification for each analyte. Results: Sera from CT26 and B16.F10 tumor-bearing mice exhibited higher average concentrations of IFN-γ, IL1-β, IL-4, IL-10, KC/GRO and TNF-α, when compared to naïve mice of the Balb/c or C57BL/6 background, respectively; however, IL-2 production was found increased in tumor-bearing Balb/c and decreased in tumor-bearing C57BL/6 mice. Though known to be promoting tumor growth, IL-6 was only measurable in three out of ten B16.F10-bearing mice and below the limit of detection in CT26-bearing mice. IL-5 and IL-12 p70 levels showed no difference between CT26-bearing and naïve Balb/c mice, whereas both cytokines were elevated in the B16.F10 model over naïve C57BL/6 mice. Conclusions: Circulating serum cytokines have been quantified in commonly used syngeneic mouse strains with and without tumor burden. These reference data provide baseline levels to compare soluble proinflammatory biomarkers suitable for assessing potential immunomodulatory effects of experimental cancer treatments in combination with other pharmacodynamic readouts. Citation Format: Kenneth Munroe, Christoph S. Eberle, Robert Mihalek, Stephen Festin. Baseline cytokine profiling in naïve and tumor-bearing Balb/c and C57BL/6 Charles River mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6025.