Reprogramming of dendritic cells by the heat shock protein-CD91 axis for cancer immunosurveillance 2497
Year: 2025
Type: article
Abstract: Description Adaptive immune responses are generated in the early stages of tumorigenesis. Tumor antigen-specific effector T cells are primed to eliminate cancerous cells prior to the emergence of palpable tumors. However, the mechanism of dendritic cell (DC) maturation and cytokine production necessary for priming T cell responses in this nascent tumor microenvironment remains undetermined. We have shown that cancer immunosurveillance is reliant on the expression of CD91, a receptor, on DCs. Interaction of CD91 with its ligands, heat shock proteins (HSPs), reprograms the DC to provide all three signals for T cell priming. In this study, we show that upon CD91 binding to HSPs, intracellular signaling pathways are initiated through the kinases AXL and Fgr. These kinases physically interact with CD91, are phosphorylated, and are required for downstream HSP-mediated cytokine production. We also show differences in CD91 signaling pathways which are dependent on the identity of the immunogenic HSP engaging CD91. The importance of AXL and Fgr in cancer immunosurveillance are tested in mouse models. These studies provide an insight into how the immune system detects and responds to emerging tumors. We predict that harnessing this CD91-mediated signaling pathway could be beneficial in enhancing cancer immunosurveillance. Funding Sources NIH T32 CA082084 NIH CA233803 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)
Source: The Journal of Immunology
Authors: James F Harkness, Robert J Binder
Institution: University of Pittsburgh
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416447985
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