Abstract 1999: Cofactor Paragon: a novel tool to analyze the tumor microenvironment using RNAseq

Abstract

Abstract The impact of cancer immunotherapy on clinical cancer care is growing rapidly. However, there are several mechanisms by which a tumor can avoid recognition and/or elimination by the immune system. Immune recognition, activation, and infiltration are each required for effective clearance of a tumor by the immune system. Impairment of any one of these mechanisms requires a different therapeutic strategy or combination of strategies to significantly address. The development of new multi-modal biomarker technologies that have the ability to provide insight into each of these factors in a cost-effective manner is essential to effectively guide treatment choice for patients and to discover new therapeutic targets. We have developed Paragon, which is an RNA sequencing based panel that utilizes novel informatics technologies to provide a comprehensive picture of a tumor’s transcriptomic and immune micro-environment. There are three distinct outputs of Paragon: measurement of the expression levels of ten immune checkpoint genes, quantification of the total mutational burden of the tumor, and the levels of infiltration of 24 different immune cell subtypes within the tumor microenvironment. These outputs collectively inform the various mechanisms that tumors use to evade recognition and clearance by the immune system. We show that Cofactor Paragon accurately reports on gene expression, mutational burden and infiltrating leukocytes compared to gold standard methods from just 20 ng of FFPE tumor RNA. We further analyze the data to show the correlation between mutational burden and infiltrating CD4+ and CD8+ T-cell levels. Finally, we show how Paragon can identify expression of genes involved in inhibitory tumor metabolism that correlate with resistance to PD-1 blockade therapy. These results position Cofactor Paragon as a novel tool that can help identify ideal therapeutic strategies in immuno-oncology. Citation Format: Ryan Bloom, Raman Talwar, Jeff Hiken, Jon Armstrong. Cofactor Paragon: a novel tool to analyze the tumor microenvironment using RNAseq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1999. doi:10.1158/1538-7445.AM2017-1999