Cytokine coordination of collective immune responses against tumors

Division Of Basic Sciences - Nci

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Abstract

We developed quantitative models of the cell-to-cell communications via cytokines amongst population of T lymphocytes. Our goal is to understand how leukocytes self-organize to decide their cell fate (e.g. between quiescence -tolerance- and death/proliferation -responses). At a fundamental level, we developed theoretical tools to analyze the heterogeneity and synchronicity of T cell responses in dense tissues. In the context of responses to tumor, we found that a critical mass of T cells existed to drive tumor rejection. Additional work is being carried out to dissect quantitatively how T cell decide collectively between tumor rejection and tumor tolerance. We also made progress in the development of a microfluidic platform (collaboration with Don DeVoe within the NI/UMD partnership) to address spatial aspects of cell-to-cell communications. This platform allows the assembly of micro-immune reactions with tumor cells, T cell and macrophages, and the observation of the ensued immune responses. The platform is also designed to allow cell recovery towards off-chip analysis (e.g. scRNAseq and FACS).