Abstract 5400: Investigating the role of IDO in MUC1 expressing breast cancers

Abstract

Abstract Breast cancer is the second most common cancer in the U.S. and contributes to 40,000 deaths a year. Breast cancer vaccines are currently being considered as a clinical intervention that may reduce the chance of metastasis and recurrence, and perhaps even function to be effective in cancer prevention. MUC1, a membrane tethered mucin glycoprotein, is over expressed in >90% of breast cancers, and therefore has been recently described as the second most targetable tumor antigen by the National Cancer Institute. There are currently ongoing trials using the MUC1 vaccine in patients with metastatic breast cancer. However, immunotherapy has had limited success because tumors have the ability to undergo immune evasion tactics. This includes expression of Indoleamine 2,3-dioxygenase (IDO) immunosuppressive enzymes. IDO was first identified in maintaining maternal tolerance towards the antigenically foreign fetus during pregnancy. Its activity is increased under pathological conditions, including during tumor development. IDO is emerging as a key player in T cell suppression and in the induction of immune tolerance to tumors. The present study is focused on understanding the role of IDO enzymatic activity on tumor development and immune function. In this study, we injected two cell lines that express IDO, and one cell line that is IDO null (MTAG, MTAG.MUC1 and IKOM, respectively). These cell lines were injected into either IDO null mice, or control c57/bk6 mice (n=3 each). We hypothesized that IDO expression in the tumor microenvironment of mice creates a pathological state of immune suppression resulting in altered tumor progression and immune function. We show that mice (whether they be IDO null or blk6) injected with IKOM cells have significantly slower tumor progression and rates of secondary metastasis as compared to those injected with IDO expressing tumor cells (p<0.05). In vitro, IKOM cells had significantly lower proliferative rates than the IDO expressing cells. Furthermore, mice injected with IKOM cells had a greater percentage of CD4+ and CD8+ T cells as compared to those mice injected with IDO expressing tumor cells. Mice injected with IDO expressing cells had a greater percentage of MDSC's characterized by the expression of gr1 and cd11b. Future studies would investigate the role of MUC1 based vaccines in combination with an IDO inhibitor, with the goal of reducing metastasis and increasing survival in patients with breast cancer. 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 5400. doi:1538-7445.AM2012-5400