Abstract 5228: Inhibition of myeloid cell PI3Kγ is a potential therapeutic approach to treat pancreatic cancer

Abstract

Abstract 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 p110γ, which is expressed exclusively by Gr1+CD11b myeloid cells, directly promotes myeloid cell invasion and consequently, tumor immunosuppression. Genetic and pharmacological suppression of PI3Kγ 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 PI3Kγ inhibitors may be useful therapeutics for pancreatic ductal carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5228. doi:1538-7445.AM2012-5228