MP55-17 EFFECT OF EPIGENETIC MODIFICATION AND IMMUNOMODULATION ON MURINE PROSTATE CANCER AND DENDRITIC CELLS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research III1 Apr 2015MP55-17 EFFECT OF EPIGENETIC MODIFICATION AND IMMUNOMODULATION ON MURINE PROSTATE CANCER AND DENDRITIC CELLS Jay Sulek, Shaoqing Zhou, Albert Petrossian, Samuel Robinson, Ekaterine Goliadze, and Georgi Guruli Jay SulekJay Sulek More articles by this author , Shaoqing ZhouShaoqing Zhou More articles by this author , Albert PetrossianAlbert Petrossian More articles by this author , Samuel RobinsonSamuel Robinson More articles by this author , Ekaterine GoliadzeEkaterine Goliadze More articles by this author , and Georgi GuruliGeorgi Guruli More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2060AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Decreased expression of highly immunogenic cancer-testis antigens (CTA) might help tumor to achieve low immunogenicity, escape immune surveillance and grow unimpeded. Our aim was to evaluate CTA expression in tumor and normal tissues and to investigate possible means of improving the immune response in a murine prostate cancer (CaP) model by using the combination of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator lenalidomide. No study to date has examined these agents in combination to treat prostate cancer or their combined impact on antigen-presenting cells (dendritic cells). METHODS Gene microarrays, quantitative PCR (qPCR) and Western blots were performed and the expressions of different CTA were compared between murine tumor and normal prostate. Effect of 5-AzaC and lenalidomide was assessed on murine CaP (RM-1 cells) and immunocompetent dendritic cells (DC). Flow cytometry, ELISA and mixed leukocyte reaction were performed to evaluate the combined effect of 5-AzaC and lenalidomide on dendritic cells. RESULTS Gene arrays and qPCR demonstrated decreased expression for most CTA-encoding genes in CaP tissue compared to normal prostate. CTA expression increased in a dose dependent fashion in RM-1 cells exposed to 5-AzaC. Quantitative PCR results were confirmed by Western blot. Flow cytometry demonstrated increased expression of co-stimulatory molecules (CD40, CD80, CD86, CD205) on DC after their treatment with 5-AzaC and lenalidomide (15%). Production of pro-inflammatory cytokines IL-12 and IL-15 by DC were increased as well. Mixed leukocyte reaction demonstrated increased ability of dendritic cells to stimulate T cells after their exposure to 5-AzaC. CONCLUSIONS Decreased expression of CTA by prostate cancer cells can be a means of escaping immune monitoring. Combination of epigenetic modification and immunomodulation by 5-AzaC and lenalidomide increased tumor immunogenicity and enhanced DC function at the same time. This combination merits further evaluation for a possible role in the treatment of advanced prostate cancer. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e679 Peer Review Report Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jay Sulek More articles by this author Shaoqing Zhou More articles by this author Albert Petrossian More articles by this author Samuel Robinson More articles by this author Ekaterine Goliadze More articles by this author Georgi Guruli More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...