Immunosurveillance mechanisms of tumors depend on the host's ability to cross-prime minute quantities of tumor antigens. We have investigated the role of tumor-derived heat shock proteins (HSPs) in transfer of tumor antigens from tumor cells to antigen presenting cells for two reasons; 1) HSPs are known to chaperone peptides in the cells. The chaperoned peptides reflect the entire antigenicity of the cell from which they are derived. 2) HSPs activate antigen presenting cells resulting in the provision of co-stimulatory molecules and cytokines. These two events require the cell surface receptor CD91 that is expressed on APCs. Here we have used a combination of CD91 inhibitors and CD91 knock-out mice to demonstrate that the HSP-CD91 interaction is crucial for developing concomitant immunity routinely seen in the tumor bearing host. This pathway is indispensable for cross-presentation when antigen levels are low. Considering that elevated levels of endogenous CD91 inhibitors 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 receptor CD91 is necessary for tumor antigen cross-priming in vivo. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B37.