Abstract 1551: Targeting myeloid derived suppressor cells as novel strategy to enhance immunotherapy in murine prostate cancer models

Abstract

Abstract Purpose: Myeloid derived suppressor cells (MDSCs) are a major component of the immunosuppressive environment responsible for immune tolerance in cancer. These cells facilitate carcinogenesis and tumor progression by impairing T and NK cells activation and contributing to regulation of angiogenesis. In current study, we evaluated whether accumulation of MDSCs occur in two murine prostate cancer models: a castrate resistant, syngenic transplantable tumor (CR Myc-Cap) and the Hi-myc transgenic tumor models. Tasquinimod is an anti-angiogenic agent tested in prostate cancer and has been found to bind to an inflammatory protein S100A9 and therefore have the potential to affect accumulation and function of MDSCs. We investigated whether tasquinimod affects the induction and function of MDSCs and facilitate vaccine therapy in these castrate resistant prostate cancer models. Experimental design: Splenocytes and blood cells were isolated from naïve and CR Myc-Cap tumor bearing mice. Blood samples were taken from Hi-myc transgenic mice and age-matched littermates at different ages. All these splenocytes and blood samples were subjected to staining with MDSCs markers, Gr1 and CD11b, and to flow cytometry analysis. CR Myc-Cap tumor bearing mice were treated with either vehicle, tasquinimod (1mg/kg), modified survivin vaccine peptide SurVaxM, or combination. Tumor growth, MDSCs accumulation and function upon treatments were monitored. Results: The peripheral MDSCs (in blood and spleen) significantly increased in tumor bearing mice. The MDSCs number increase correlated with disease progression in the transgenic model. Low doses of tasquinimod (1-5mg/kg) did not change the CD11b+Gr1high MDSCs number, but CD11b+Gr1high, CD11b+Gr1int, CD11b+Gr1− cells were differently accumulated in vehicle or tasquinimod treated mice. Tasquinimod in vivo treatment reduced peripheral CD11b+Gr1int, CD11b+Gr1− cells number. Low doses of tasquinimod have minimal effect on CD11b+Gr1high MDSCs function and did not enhance the SurVaxM vaccine therapy in CR Myc-Cap model.Conclusions: In summary, our study demonstrates MDSCs accumulation in two prostate cancer models and suggests that MDSCs may contribute to immune tolerance in prostate cancer. The study also suggests low dose tasquinimod affect maturation of MDSCs into other immunosuppressive cell types (CD11b+Gr1int, CD11b+Gr1−). Higher doses of tasquinimod (≥10mg/kg) are being tested for their potential to affect MDSCs accumulation and function in prostate cancer models. 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 1551. doi:1538-7445.AM2012-1551