# Intercepting the Evolution of Pro-Tumoral Myeloid Cells During the Initiation of Oral Cancer

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $54,774

## Abstract

PROJECT SUMMARY/ABSTRACT
Earlier detection and treatment of human papillomavirus (HPV)-negative head and neck squamous cell
carcinomas (HNSCC) has the greatest potential to improve overall survival rates, which have remained stagnant
at around 50% for several decades. Patients with HPV-negative HNSCC often have a clinical history of oral
epithelial dysplasia (OED), but it remains unclear which lesions will progress to cancer. Through comprehensive
sequencing of these tumors, it is known that a common (about 20%) genetic alteration event is the amplification
at locus 3q26.3, which harbors oncogene SOX2 (SRY-box transcription factor 2). Previous research revealed
that SOX2 inhibits a critical immune sensing pathway by degrading stimulator of interferon genes (STING)
protein in HNSCC cancer cells. The activation of the STING pathway is essential for establishing a spontaneous
anti-tumor immune response, as it promotes the presentation of tumor antigens on the surface of myeloid cells,
leading to the activation of cancer-killing T cells. It remains unclear how STING signaling in tumor-resident
immune cells may be impacted during SOX2-driven malignant transformation. To investigate this, we have
developed a preclinical mouse model to study the transition from OED to HNSCC. Upon high-dimensional
analysis of the immune landscape, we find a unique myeloid cell phenotype that suppresses anti-tumor immune
response. This study will utilize a multipronged approach to investigate the mechanism by which myeloid cells
in SOX2-positive lesions develop terminal suppressive phenotypes. We will test pharmacological and genetic
strategies to intercept the evolution of these pro-tumoral myeloid cells. Ultimately, this project will provide a high-
resolution atlas of functionally distinct myeloid cell subsets in precancerous lesions and identify key interception
points for therapeutic intervention.

## Key facts

- **NIH application ID:** 10903099
- **Project number:** 1F31DE033922-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Hulya Taner
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $54,774
- **Award type:** 1
- **Project period:** 2024-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903099

## Citation

> US National Institutes of Health, RePORTER application 10903099, Intercepting the Evolution of Pro-Tumoral Myeloid Cells During the Initiation of Oral Cancer (1F31DE033922-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10903099. Licensed CC0.

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