The goal of our lab is to develop novel macrophage targeted therapies for the treatment of solid tumors with special focus on neuroblastoma and pancreatic ductal adenocarcinoma. Our laboratory has focussed on the study of signal transduction pathways which promotes recruitment and polarization of macrophages into the immunosuppressive phenotype in solid tumors.
Our lab has identified a novel macrophage autonomous pathway involving Rac2 and Syk kinase downstream of the provisional integrins, a4b1 and avb3 that controls immunosuppressive macrophage differentiation in tumor growth and metastasis. Our recent work has demonstrated Syk as a novel immuno-oncology target which plays a crucial role in the control of macrophage-mediated immune suppression and the inhibition of anti-tumor immunity in the lung carcinoma model. We have shown that genetic or pharmacologic inhibition of Syk and/or PI3Kgamma in macrophages promotes a proinﬂammatory macrophage phenotype, restores CD8+ T-cell activity, destabilizes HIF under hypoxia, and stimulates an antitumor immune response in various syngeneic mouse models.
We are now investigating 1) the mechanisms which promote the recruitment of macrophages in MYCN amplified and non-MYCN amplified neuroblastoma tumors 2) if macrophage targeted therapies in combination with immune checkpoint inhibitors or radiotherapy can improve survival of patients in neuroblastoma.In parallel 3) we are exploring the role of Syk kinase in progression of pancreatic carcinoma.