Max Krummel, University of California, San Francisco, USA
Talk Title: Visualizing tumor immune interaction in real time
Important discoveries come from fundamental research and ‘How does this work?’ questions. For the past 20 years, I have studied mechanisms that regulate T cell responses and therefore regulate immune function, using cutting-edge real-time imaging methods to ask these kinds of questions. As a graduate student, I developed expertise in the generation and use of monoclonal antibodies targeted to costimulatory and inhibitory molecules on T cells. In this work, I generated antibodies to CTLA-4, which not only identified an inhibitory pathway of T cell regulation but also could be used to trigger or block that pathway. I subsequently applied these antibodies toward upregulating T cell responses to antigens in vivo and then toward augmenting immune responses to tumors. That approach led in time to the development of human antibodies of the same type, a therapy now named ‘ipilimumab’, now FDA approved and widely used for treatment of melanoma and other cancers. I am a poster child for the assertion that basic studies yield clinically-relevant results.
My lab now focuses on figuring out how immune systems, collections of cells in complex tissues, work. Our work capitalizes on using fluorescent proteins to track information processing by the immune system using real-time imaging and have profited from considerable investments in developing novel imaging approaches. In addition, my lab emphasizes the use of fluorescent imaging approaches to understand how information is exchanged in the dense cellular milieu of organs. These approaches are revealing how motile immune cells ‘search’ their environment for critical information. They are also revealing unexpected dynamics of the assembly of complexes of lymphocytes—clusters and temporally ordered aggregates of cells. One exceptionally useful approach that we’ve developed is the generation of spontaneous models of breast cancer in which the stromal cells that interact with tumors become fluorescent by virtue of the uptake of very stable fluorescent protein variants. This enables us to focus on specific phagocytes in the tumor microenvironments and begin to characterize them as primary players in transmitting signals to lymphocytes and regulating disease outcome.
We continue to seek ways to understand basic biology and translate that knowledge into mechanisms for improving selectivity in the immune response.
Web Homepage: http://pathology.ucsf.edu/krummel/
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