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The pathogenic role of tumor-associated macrophages in Hodgkin lymphoma

Robert Kridel

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Canadian Institutes of Health Research (CIHR)
Lymphomas are malignant tumors of a subset of white blood cells, so-called lymphocytes. Among lymphomas, Hodgkin lymphoma is the most common subtype in young people in the Western world. Fortunately, most of the patients suffering from this disease are cured by current treatments. Nonetheless, about 20% of all patients die from treatment failures or late complications related to treatment. Our goal is to better understand the biological underpinnings behind treatment failure. Tumor biopsies from patients with Hodgkin lymphoma contain numerous cells that are part of an inflammatory reaction of the immune system that is unsuccessful at eradicating the lymphoma. In particular, we are interested in macrophages, a cell type that takes part in this reaction. The main function of macrophages is to protect our body by engulfing foreign organisms such as bacteria. But they are also present in the biopsies of many tumors and there is increasing knowledge documenting that these tumor-associated macrophages are beneficial for tumor survival and hence detrimental for patients. By our own work, we know that those Hodgkin lymphoma patients whose biopsies contain increased numbers of macrophages often present with recurrence after treatment and die. This project aims at describing the exact function of tumor-associated macrophages in Hodgkin lymphoma. We want to find out what signals macrophages send to tumor cells and vice versa, entertaining a potentially devastating crosstalk of these cell types for affected patients. The ultimate goal will be to target these signals and prevent macrophages from supporting the tumor. Our findings could lead to a completely novel treatment approach by targeting not only the tumor cells themselves, but also the environing immune cells that nurture lymphoma cells.

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