Cytokine coordination of collective immune responses against tumors

我们通过细胞因子在T淋巴细胞群中建立了细胞间通讯的定量模型。我们的目标是了解T细胞如何自我组织来决定它们的细胞命运（例如，在沉默-耐受-和死亡/增殖-反应之间）。在基础水平上，我们开发了理论工具来分析致密组织中T细胞反应的异质性和同步性。在对肿瘤的反应中，我们发现存在临界质量的T细胞来驱动肿瘤排斥反应。更多的工作正在进行，以定量剖析T细胞如何在肿瘤排斥和肿瘤耐受之间共同决定。我们还在开发一个微流体平台（与NI/UMD合作伙伴关系中的Don DeVoe合作），以解决细胞间通信的空间问题。该平台允许与肿瘤细胞、T细胞和巨噬细胞组装微免疫反应，并观察随之而来的免疫反应。该平台还允许细胞恢复到片外分析（例如scRNAseq和FACS）。

We developed quantitative models of the cell-to-cell communications via cytokines amongst population of T lymphocytes. Our goal is to understand how T cells 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 are also in the process of developing 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).