# Defining immune-evasive mechanical signaling in head and neck cancer

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $653,172

## Abstract

Project Summary
Head and neck cancer squamous cell carcinomas (HNSCC) are the seventh most common cancers globally
and are associated with poor survival rates. Pharmacological treatments for HNSCC remain largely ineffective
and improving therapies requires the identification of novel factors that modulate not just the tumor but also the
surrounding permissive oral microenvironment. Aging is a variable tightly associated with HNSCC development
and is linked to tissue alterations and defective immune responses. However, while older chronological age is
associated with tumor development and elderly HNSCC patients exhibit worse five-year survival, very little is
known about the molecular mechanisms by which aging contributes to the etiology of HNSCC. The goal of this
proposal is to define signals associated with HNSCC progression in aged tissues with the hope to uncover
targetable mechanisms that may offer new therapeutic avenues. To test the influence of age on HNSCC, we
optimized syngeneic orthotopic tongue xenograft models of HNSCC and have observed more rapid tumor
growth in old animals, with tumors exhibiting an age-associated, immune evasive and transcriptionally-distinct
tumor cell states. We have found that these age-associated alterations correlate with increased extracellular
matrix levels that we hypothesize the mechanical properties of old tissues direct distinct mechanosensitive
signals. Our observations suggest that the mechanical-effector YAP, a transcriptional regulator mediating
Hippo pathway signaling that has pro-tumorigenic functions in HNSCC, is linked to age-associated
tumorigenesis. We propose to examine the relationship between aging, extracellular matrix dynamics, YAP
activity and YAP-directed functions, including immune evasion. We further plan to compare matrix dynamics
and tissue elasticity across mice of different chronological age and test how increasing collagen levels or
reducing collagen crosslinking affects tumorigenic behavior. We will further test the consequences of inhibiting
YAP activity in age-associated tumors, profiling accompanying transcriptional and cellular changes. Finally, we
will test how reintroducing an absent chemokine program regulated by YAP that is repressed in the old tongue
microenvironment impacts tumor growth and tumor lymphocyte infiltration. Data collected from our study will
provide a comprehensive assessment of age-associated mechanical signals and offer new insight into
mechanisms that may direct the heterogenous lymphocytic functions observed in HNSCC.

## Key facts

- **NIH application ID:** 10793249
- **Project number:** 1R01DE033519-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** MARIA A. KUKURUZINSKA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $653,172
- **Award type:** 1
- **Project period:** 2024-06-06 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10793249

## Citation

> US National Institutes of Health, RePORTER application 10793249, Defining immune-evasive mechanical signaling in head and neck cancer (1R01DE033519-01). Retrieved via AI Analytics 2026-06-15 from https://api.ai-analytics.org/grant/nih/10793249. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*