Characterization of immune cell populations in syngeneic murine tumor models.

Abstract

Immunocompetent murine models are important tools for preclinical evaluation of immunotherapies. Here, six different immunocompetent tumor models based on four different cell lines were characterized, including metastatic lung cancer (CMT 167), triple-negative breast cancer (4T1), pancreatic cancer (KPCY), and colon cancer (MC38). The tumors were implanted subcutaneously or orthotopically before the animals were treated with anti-PD1 checkpoint inhibitor. A range of innate and adaptive immune cells were then quantified by flow cytometry of single-cell suspensions from the tumors. Furthermore, confocal laser scanning microscopy was used to quantify the density and distribution of T-cells in frozen sections. A model-dependent cellular immune landscape was observed, with variable responsiveness toward anti-PD1, ranging from the most responsive MC38 colon cancer model to the least responsive 4T1 breast cancer model. The study provides an overview of the immune landscape of these tumor models, and a foundation for further elucidation of pro-tumor and anti-tumor mechanisms behind heterogeneous responses towards immunotherapies.