CD91 and its ligand heat shock proteins regulate dendritic cell functions during immunosurveillance of emerging tumors

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B154
Abstract ID: 4611

Presenting Author:
Devanshi A. Nayak , Graduate Student at Univ. of Pittsburgh

Abstract:

Dendritic cells (DCs) play a pivotal role in initiating and modulating responses against nascent tumors. This study investigates how immunogenic heat shock proteins (HSPs), particularly glycoprotein 96 (gp96), efficiently chaperone minute amounts of peptides during early tumor development to evoke antigen-specific immunity. Tumor-derived gp96 is endocytosed by CD91, a receptor on DCs that is crucial for cross-priming T cells. Here we generated mouse models with DC-specific CD91 deficiency (CD11c^Cre, XCR1^Cre, Mgl2^Cre) and a system to track dispersal of tumor-derived gp96. Our data suggests that CD91 expression on type 1 conventional DCs (cDC1) is essential for uptake of gp96 during cancer immunosurveillance. While gp96⁺ cDC1s contribute to early tumor control, sustained and long-term tumor control is facilitated by other gp96⁺ cross-priming DCs (CD11b⁺ cDCs) through intercellular transfer of gp96. Single cell analysis of antigen-presenting cells (APCs) in tumor-draining lymph nodes illustrates that CD91 promotes T cell priming, while downregulating immune regulatory pathways. Engagement of CD91 initiates co-stimulation, cytokine production and cross-presentation of HSP-chaperoned peptides establishing it as a primary mechanism immunosurveillance. Understanding the role of CD91⁺ DCs in cancer immunosurveillance holds significant implications for cancer prognosis and therapy, revealing the division of labor among APCs in the successful elimination of cancer cells.