Core B: Animal Model and Immunotyping Core

Project Summary Our preliminary data suggested a shared paradigm for the impact of the STING-IFN-β/TGFβ/IL-17 cytokine network on tumor progression and responses to therapy, which transcends the tissue origins of each cancer. Our goal, to unravel the crosstalk and define the paradigms, necessitates standardization of the protocols and procedures used by each constituent project, in order to unify our approaches in establishing preclinical tumor models and measuring tumor responses to therapy. Our ability to reach meaningful conclusions critically hinges on comparable execution of in vivo studies. Furthermore, a common readout shared by all three constituent projects is the inflammatory status in the TME. While immune-supportive inflammation (CD8, Th1, and dendritic cells) is associated with favorable responses to immune checkpoint inhibitor therapy, an immune-suppressive inflammatory environment (immature myeloid cells and fibroblasts) can antagonize anti-tumor immunity. Accurate detection, characterization and quantification of multiple cell types by flow cytometry and single-cell sequencing are crucial for assessing the state of intra-tumoral inflammation. A shared infrastructure that enables reliable analysis of the TME is essential for studying cytokine crosstalk. Taken together, the Animal Model and Immunotyping Core will be charged with two missions. First, the Core will provide technical and experimental infrastructure to enable uniform and standard in vivo analyses, including preclinical assessment of cancer therapeutics and characterization of the TME. Secondly, the Core will function as a hub for interaction among the constituent projects, including analytics assistance and scientific consultation on analyses of the TME.