Abstract PR01: The heat shock protein-CD91 pathway is necessary for tumor immunosurveillance

Abstract

Abstract Many tumors are capable of generating immune response in the bearing host. Since tumors lack the typical (foreign) PAMPs that provide signal 2 for T cell priming, the mechanism of how concomitant immunity is established remains a mystery. We provide evidence here that, heat shock proteins (HSPs), when released into the tumor microenvironment, is the immunogen necessary for tumor immunosurveillance. This response requires CD91- the endocytic and signaling receptor for the immunogenic HSPs. In our study, we generated CD11c-specific CD91 knockout mice and showed that transplantable tumors grew faster in those knockout mice, compared to wild type mice. In addition, we abrogated the interaction of tumor-derived HSP with CD91 in vivo by over-expression of Receptor Associated Protein (RAP), an endogenous inhibitor of CD91. The loss of CD91 funtion through antagonism or its deletion was shown to negatively affect cross-priming. While initial studies were performed on transplantable tumors, these experiments have now been carried out in chemically induced tumor models. In summary, our study demonstrates that the HSP-CD91 pathway is critical for establishment tumor immunity. Considering that elevated RAP levels have been reported in colon cancer patients, we propose a novel mechanism of immune evasion for tumors expressing competing ligands for immune receptors such as CD91. Citation Format: Yu Jerry Zhou, Robert J. Binder. The heat shock protein-CD91 pathway is necessary for tumor immunosurveillance. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr PR01.