Cytokines are central immunoregulators that play key roles in both the upregulation (initiation) and downregulation (turning off) immune responses. They are involved in the control of proliferation, cell survival, differentiation, immune cell activation, cell migration and death. In tumors, cytokines can be expressed by immune cells, stromal cells (fibroblast and endothelial cells), and tumor cells. Depending on the inflammatory state of the tumor microenvironment, they can modulate either an antitumoral response or help to induce cell transformation and malignancy. There is ample literature available for cytokine profiles of patient tumor and serum samples but few reports from mouse syngeneic models of cancer. Here, we describe our studies evaluating the cytokine profiles (systemic and intratumoral) of common syngeneic tumor models. We generated the profiles of proinflammatory cytokines (IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 p70, interferon-gamma, CXCL-1 and tumor necrosis factor-alpha) for the most commonly used syngeneic models in immuno-oncology (MC38, B16F10, CT26, Colon26, Renca and 4T1). Data from naive mice and cell lines help to understand any changes to these cytokines in tumor-bearing animals naive to treatment. Additionally, we have treated MC38 tumor-bearing animals with two anti-mouse PD-1 clones and evaluated the cytokine responses at different time-points post treatment. We observed localized changes to the levels of some cytokines in the tumor microenvironment, followed by systemic cytokine alterations. The pretreatment cytokine profiles may help us with model selection to investigate immune and inflammatory modulators. In addition, understanding the cytokine responses during and after treatment can also provide insight into the mechanisms of action of immunomodulatory agents and provide hypotheses for combinations. Together, these findings could provide early information about immune infiltrates after treatment, and in the future could be of use as possible biomarkers of response or safety.
Citation Format: Jolanta Dubauskaite, Laura Bradshaw, Ashley Merlino, Xianhui Rong, Connie Gee, Glenn Dranoff, Maria Pinzon-Ortiz. Proinflammatory cytokine profile of syngeneic models [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B79.