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.
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