UC San Diego

Tumor inflammation plays a significant role in initiating and perpetuating tumor growth, angiogenesis and metastasis. While normal inflammatory responses aid in wound healing, fighting infections, and destroying pathogens, tumor inflammation is self-perpetuating and plays a role in facilitating the disease, in part by inducing immunosuppression. Gr1+CD11b+ myeloid cells are the most prevalent inflammatory cells found in tumors, where they directly promote tumor angiogenesis and immunosuppression. Recent studies in our laboratories have shown that the phosphatidylinositol 3-kinase (PI3K) catalytic subunit isoform p110 gamma, which is expressed exclusively by Gr1+CD11b myeloid cells, directly promotes myeloid cell invasion and consequently, tumor immunosuppression. Genetic and pharmacological suppression of PI3K gamma activity substantially reduces myeloid cell trafficking to orthotopic Pdx1Cre;Kras+; p53+/- and other pancreatic ductal carcinomas, reduces expression of immunosuppressive factors, and inhibits pancreatic tumor growth and metastasis. These studies indicate that PI3K gamma inhibitors may be useful therapeutics for pancreatic ductal carcinoma