Abstract 498: Integrating bulk and spatial profiling technologies for the discovery of RNA and protein biomarkers in muscle invasive bladder cancer

Abstract

Abstract Muscle-invasive bladder cancer (MIBC) is an aggressive disease with limited therapeutic options. Although immunotherapies are approved for MIBC, the majority of patients fail to respond, suggesting the existence of complementary immune evasion mechanisms underscoring the need for comprehensive immune profiling of patient tumor samples. The PPARγ pathway constitutes a tumor-intrinsic mechanism underlying immune evasion in MIBC. Immune cell-infiltration is controlled by activated PPARγ, which in turn inhibits expression/secretion of inflammatory cytokines. Clinical data sets indicate that PPARγHigh impairs CD8+ T-cell infiltration and confers partial resistance to immunotherapies. Here, we report a comprehensive biomarker study aimed at identifying a single, highly multiplexed platform for profiling the tumor microenvironment in clinical-type specimens as formalin-fixed, paraffin-embedded (FFPE) samples. A cohort of PPARγHigh and PPARγLow muscle invasive bladder cancer samples were used for the technology assessments. Gene expression patterns were measured using a combination of research use only genomics and spatial genomic technologies to determine concordance including RNA-seq, spatial in situ hybridization (GeoMx™ Digital Spatial Profiler) and IO360. We determined that multiple RNA and protein-based technologies were able to accurately characterize the immune phenotypes of PPARγHigh tumors. However, the GeoMx™ technology was ideal for precious samples since it digitally quantifies target abundance while maintaining spatial resolution in only two FFPE slides. GeoMxTM DSP technology is for Research Use Only and not for use in diagnostic procedures. Citation Format: Zhaojie Zhang, Subhasree Das, Manav Korpal, Pavan Kumar, Jingjing Gong, Yan Liang, Margaret Hoang, Joseph Beecham, Victoria Rimkunas. Integrating bulk and spatial profiling technologies for the discovery of RNA and protein biomarkers in muscle invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 498.