CCBIO seminar: Jonathan M. Irish
Decoding human tumor microenvironments and healthy tissues using high dimensional single cell mass cytometry
Jonathan M. Irish
Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA
New generations of treatments have successfully targeted cancer cell signaling and modulated anti-cancer immunity to significantly improve outcomes for advanced stage malignancies. Such treatments focus on understanding what is specifically abnormal about cells in the disease context and employing these differences as biomarkers or targets. These clinical cell biology insights have paralleled advances in single cell technology and sparked intense study of the cellular mechanisms driving therapy response and resistance . These responses are governed by an evolving milieu of cancer, immune, and stromal cell subpopulations. Mass cytometry is particularly well suited to tracking cells in complex tissues because 35+ measurements can be made on each of hundreds of thousands of cells per sample, allowing all cells detected in a sample to be characterized for cell type, signaling activity, and functional outcome . This talk will survey the use of mass cytometry for systems level characterization of cells in healthy human tissues, including blood, bone marrow, and tonsillar tissue, as well as diseases including melanoma, glioblastoma, lymphoma, leukemia, bone marrow failure and myelodysplastic syndromes, and graft vs. host disease. The state of the art in single cell tumor immunology will be discussed, including tissue collection, technical and biological quality controls, analysis of cell signaling (phospho-flow), computational analysis, and integration of different experimental and clinical data types . Ex vivo analysis of human tumor cells complements both in vivo monitoring, which generally measures far fewer features or lacks single cell resolution, and laboratory models, which incur cell type losses, signaling alterations, and genomic changes during establishment. Mass cytometry is on the leading edge of a new generation of cytomic tools that work with small tissue samples, such as fine needle aspirates or blood draws, to monitor changes in rare or unexpected cell subsets during cancer therapy. This approach holds great promise for dissecting cellular microenvironments, monitoring how treatments affect tissues, revealing cellular biomarkers and effector mechanisms, and creating new treatments that productively engage the immune system to fight cancer and other diseases.
1 Greenplate, AR, Johnson, DB, Ferrell, PB, Irish, JM. 2016. Systems immune monitoring in cancer therapy. Eur J Cancer 61:77-84.
2 Leelatian, N, Diggins, KE, Irish, JM. 2015. Characterizing phenotypes and signaling networks of single human cells by mass cytometry. Methods Mol Biol 1346:99-113.
3 Irish, JM, Doxie, DB. 2014. High-dimensional single-cell cancer biology. Curr Top Microbiol Immunol 377:1-21.
Chairperson: James Lorens, CCBIO