Tolerogenic Dendritic cells are not well defined as a DC subtype and the factors that dictate how well tolDCs will function as a cell therapy are relatively unknown. Most tolDC cell therapies have not show clinical success due to high patient variability of responsiveness to classical immunomodulators. We want to see what factors drive TolDCs towards productive, Treg inducing phenotypes. We have two approaches to understand this problem. First, using immunosuppressive cancer cell lines, we are screening for novel immunomodulatory molecules or mechanisms. Cancer cells are known to generate tolDCs, but the mechanisms are relatively unknown. The second strategy is to analyze the small population of patients whose native DCs show high responsiveness to tolerizing therapies. We are looking for methods to identify these responder patients and isolate the factors that contribute to this responsive phenotype.
