Project 170561

A number of bacterial and viral products have been shown to reduce tumor growth in models of cancer and in clincal trials, however we have a poor understadning of how these work. Mast cells are immune cells often associated with allergic disease. They are increased in numbers around solid tumors and could regulate local anti-tumor immunity. Mast cells have been well studied in a variety of disease models and they are known to be able to initiate the development of effective immunity against a number of pathogens. Preliminary studies in Dr. Marshalls laboratory have recently shown that when activated with certain bacterial products, mast cells can reduce the rate of tumor growth in models of melanoma and lung cancer. Mast cells appear not to kill tumor cells directly but to recruit other cell types and modify the bodys response to tumors in a way that prevents tumor growth. There are three major objectives to the current study. The first will examine how mast cells might modify the immune response to tumors by recruiting immune cells to tumor sites. The second will examine how mast cells might prevent tumors developing their own blood supply or enhance their susceptibility to immune cell killing through production of a protein called interferon-gamma. A third series of studies will examine how mast cell production of a protein known as interleukin-6 can increase anti-tumor immunity. These studies will allow us to assess the potential of using selective mast cell activation in cancer therapy and to better understand the mechanisms whereby certain bacterial products prevent tumor growth

investigating mast cell-mediated tumor growth inhibition through immune cell recruitment and cytokine production