JENNA NEWMAN PHD, THERESA CHU, ASHLEY REID, AND MATTHEW BROWN
Jenna studies mutation-derived tumor antigens (MTA), and MTA-specific T lymphocytes, with the hope of better understanding the interaction between malignant cells and the host immune system. We employ multiple high-throughput techniques such as exome and transcript sequencing, as well as single-cell mass cytometry to understand the phenotype, function, trafficking as well signal transduction and transcriptional and epigenetic regulation of tumor-antigen specific T cells, including MTA-specific T cells. Ultimately, the knowledge gained in the course of our studies will facilitate the safe and effective use of the current class of cancer immune therapies, and aid in the design of more effective next generation immune therapies.
Matt studies T cell responses to MSI high human tumors: Although immune checkpoint blockade has been a successful treatment strategy for many patients with mismatch repair deficient (MMRd) cancers due to their high tumor mutational burden, up to 60% of patients are resistant to treatment, creating an urgent clinical need for novel immunotherapeutic strategies to prevent and treat MMRd tumors. This study will build off preliminary work from our laboratory showing frameshift (fs) neoantigen peptides encoded by insertion/deletion mutations in MMRd lesions are recognized by T cells in patient blood by i) tracing the spatiotemporal landscape of fs-neoantigen expression and fs-specific T cell infiltration into tumors throughout human MMRd cancer development and ii) assessing T cell dysfunction and immunosuppressive pathways enriched in MMRd lesions that evade antitumor T cell surveillance and progress to malignancy. This effort is leveraging in vitro T cell immunogenicity studies and ex vivo spatial and genomic analyses to ultimately reveal neoantigen vaccine targets to prevent MMRd tumors and elucidate biomarkers/therapeutic targets for lesions resistant to current immunotherapeutic approaches.