Abstract B24: Identification of immunosuppressive networks in colon cancer

Abstract

Abstract Despite important improvements over the past two decades in preventive screening and targeted therapies, colorectal cancer remains the third major cause of cancer-related deaths in the U.S. The majority (~85%) of colon cancer tumors are non-immunogenic, i.e. they lack a significant number of infiltrating cytotoxic T cells, and are typically unresponsive to the new immune-checkpoint inhibitor based therapies that have dramatically changed the way we treat many cancer patients. These non-immunogenic colon cancer tumors are also characterized by chromosome instability and are microsatellite stable (MSS). Microsatellite instable (MSI) tumors present a greater variety of antigens and are significantly more immunogenic. We analyzed the paired mRNA and microRNA RNA-Seq expression profiles contained in The Cancer Genome Atlas (TCGA), representing MSS colon cancer, MSI colon cancer, and normal colon tissues. These expression profiles reflect the heterogeneity of the tumor samples, with MSI samples showing distinct immune cell signatures. Integrative analysis of mRNA and microRNA expression patterns revealed signaling networks that may represent, in part, the molecular mechanisms by which cancer cells modulate the host response to create an immune privileged microenvironment. These findings could result in a novel therapeutic avenue, targeting a tumor's ability to suppress the immune response, addressing a critical barrier to treatment for non-immunogenic tumors. Citation Format: Anne E. Sarver, Aaron L. Sarver, Subbaya Subramanian. Identification of immunosuppressive networks in colon cancer. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B24.