# CD91 and cancer immunosurveillance

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $347,794

## Abstract

The immune system recognizes aberrant cells and eliminates them prior to emergence of nascent tumors. This
prevents progression of many malignancies. In the absence of such immunity in mice or humans, multiple and
frequent tumors are generated. Current immunosurveillance model involves the priming of T cell and NK cell
immunity. The gap in knowledge in this model is raised in two questions; (1) What is the molecular mechanism
for cross-priming T cell responses in the context of the negligible amount of antigen available at the early
stages of nascent tumor development? (2) What is the stimuli for co-stimulation of T cell priming and activation
of NK cells. Our work has demonstrated that tumor-derived heat shock proteins (HSPs), introduced during
vaccination, are super-efficient at cross-presentation of limited amounts of their chaperoned tumor (peptide)
antigen. HSPs are also capable of initiating signals for co-stimulation. Both events require the HSP receptor,
CD91, expressed on dendritic cells and together allow for priming potent tumor-specific T cells. The release of
cytokines by DCs stimulated with HSPs enhances the T cell responses and activates NK cells. Our hypothesis
is that when tumor antigen levels are limiting, as in nascent emerging tumors, the HSP-CD91 pathway is
essential for cross-priming of anti-tumor immune responses. In humans, immune responses to cancer are
influenced by variable expression levels of CD91 and its polymorphism, driving the clinical and translational
relevance of this proposal. In this application we will determine how CD91 serves as an essential conduit for
initiating responses for cancer immunosurveillance.

## Key facts

- **NIH application ID:** 10308038
- **Project number:** 5R01CA233803-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Robert J Binder
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $347,794
- **Award type:** 5
- **Project period:** 2019-12-16 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10308038

## Citation

> US National Institutes of Health, RePORTER application 10308038, CD91 and cancer immunosurveillance (5R01CA233803-03). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10308038. Licensed CC0.

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