2017 IO Featured Talks » Targeting Macrophage PI3kinase Signaling to Suppress Tumor Progression

Part 1

Part 2

Judy Varner, PhD
Professor of Pathology and Medicine
UC San Diego Moores Cancer Center

The Varner Lab studies the molecular mechanisms by which the tumor microenvironment promotes tumor growth and metastasis. Our most recent focus is on understanding the roles that inflammation, angiogenesis and lymphangiogenesis play in promoting tumor growth and spread. Tumor inflammation promotes angiogenesis, immunosuppression and tumor growth, but the mechanisms controlling inflammatory cell recruitment to tumors are not well understood. Our lab recently found that chemoattractants activating G-protein coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and Toll-like/IL-1 receptors (TLR/IL1Rs) all promote tumor inflammation by activating the PI3-kinase isoform p110γ in Gr1+CD11b+ myeloid cells. PI3kinase gamma then activates integrin α4β1 to promote myeloid cell trafficking to tumors and subsequent angiogenesis and immunosuppression. We have determined that antagonists of PI3kinase gamma and integrin α4β1 are potent suppressors of tumor inflammation, angiogenesis, growth and metastasis.