Abstract LB-117: Phenotype and function of tumor-infiltrating macrophages and B cells in a novel humanized mouse model (NSG-HIS) for ovarian cancer

Anti-cancer treatments are often highly effective in human tumor xenografts grown subcutaneously in immune deficient hosts such as athymic (nude) or severe combined immune deficient (SCID) mice. However, such preclinical results are frequently followed by failure or limited activity of the drug/therapy in clinical trial, prompting the development of more sophisticated animal models engrafted with fully human immune system (HIS). We reconstituted NOD-Scid-IL2Rγcnull (NSG) mice with cord blood-derived CD34+ cells and 12 to 16 weeks after transplantation NSG-HIS mice were injected with human ovarian tumor cells (OVCAR5) orthotopically (io), subcutaneously (sc), or both (io/sc). Although sc tumor growth was the fastest in the absence of human immune system, four weeks after tumor implantation the average sizes of sc, io and sc/io tumors were similar across all NSG-HIS groups (0.3cm3); regardless of the tumor site, all tumors were infiltrated with human B cells, T cells and macrophages. However, sc tumors contained proportionally more human B cells and macrophages than io tumors. Macrophages infiltrating sc and io, but not sc or sc/io tumors, exhibited an IL10high immunosuppressive phenotype. Io tumor-infiltrating macrophages expressed the highest levels of CD32 (FcγRII) and mannose receptor (CD206), and the lowest level of CD64 (FcγRI) compared to macrophages infiltrating sc or io/sc tumors. Finally, io tumors were infiltrated with less human B cells than all the other tumors; B cells from tumor-bearing mice presented an altered phenotype compared to non tumor-bearing animals, characterized by the upregulation of plasma and activation markers and the production of IgM and IgG. Our results support the hypothesis that the location of the tumor implantation impacts the phenotype and function of human tumor cell infiltrate. The novel NSG-HIS mouse model of ovarian cancer may help understanding the role of tumor microenvironment during tumor development. 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 LB-117. doi:1538-7445.AM2012-LB-117