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- W3043280052 abstract "Macrophages play key roles in promoting immune suppression, tumor growth, and resistance to therapy. Our recent studies show that tissue-resident macrophages (TRM) as well as bone marrow-derived macrophages (BMDM) play critical but unique roles in promoting tumor growth. While BMDM are recruited to tumors in a PI3Kγ, Integrin α4, and CCR2-dependent manner, TRMs accumulate in tumors independently of integrin α4, PI3Kγ, or the trafficking receptor CCR2. Gene expression and functional studies indicate that tumor-derived TRM are highly proliferative, immune suppressive, and distinct from BMDM. We show that TRM develop from macrophage progenitors that are abundant in tumors but not in normal tissues; purified progenitors differentiate into macrophages that potently stimulate tumor growth when adoptively transferred into mice. Notably, we found that the lipid kinase PI3Kγ promotes immune-suppressive polarization of TRM and BMDM. Inhibition of PI3Kγ repolarizes macrophages, induces dendritic cell maturation, and stimulates CD8+ T-cell recruitment to tumors and activation. Inhibition of PI3Kγ also synergizes with checkpoint inhibitors and chemotherapeutics to promote tumor regression and immunologic memory, leading to sustained tumor suppression. Our studies identify PI3Kγ as a valuable target for immune therapy of solid tumors. Citation Format: Judith A. Varner. Control of tumor immune suppression by macrophage PI3Kγ regulated pathways [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr IA25." @default.
- W3043280052 created "2020-07-23" @default.
- W3043280052 creator A5084979875 @default.
- W3043280052 date "2020-04-01" @default.
- W3043280052 modified "2023-09-27" @default.
- W3043280052 title "Abstract IA25: Control of tumor immune suppression by macrophage PI3Kγ regulated pathways" @default.
- W3043280052 doi "https://doi.org/10.1158/2326-6074.tumimm18-ia25" @default.
- W3043280052 hasPublicationYear "2020" @default.
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