Systems biology of the tumor immune microenvironment

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Systems biology of the tumor immune microenvironment Project Summary- Research activities proposed for the extension year will exploit syngeneic murine cancer models established with U54 funding (Projects 1, 3) and recent single cell epigenetic/multiomic and spatial transcriptomic technologies deployed at our Center (Projects 1, 2, Shared Resource Core), enabling experimental and computational modeling of tumor-immune interactions with high fidelity to human tumor biology and at rich single cell and spatial resolution. Below we outline six major activities for the extension year, each led by a Center investigator and contributing to the original specific aims of our U54 proposal. 1. Modeling T cell, stromal, and cancer cell co-evolution in melanoma (Project 1). 2. Learning gene regulatory programs governing tumor-associated T cell states (Project 1). 3. Spatial analyses of Treg cell-mediated cellular communications in the lung adenocarcinoma microenvironment (Project 2). 4. Immune surveillance of metastasis in a syngeneic murine lung adenocarcinoma model (Project 3). 5. Tissue mimetic modeling of the response of metastatic lineages to nutrient gradients (Project 3). 6. Computational integration of single cell RNA and ATAC sequencing data (Shared Resource Core). .