# Oral Microbiota and Toll-Like Receptor Pathways in Head and Neck Cancer

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2020 · $233,250

## Abstract

PROJECT SUMMARY
 Head and neck squamous cell carcinoma (HNSCC) remains a lethal disease despite concerted efforts to
improve its diagnosis and treatment. Although smoking, drinking, and HPV infection are closely linked to
HNSCC, emerging evidence also suggests that changes in the human microbiome are associated with
HNSCC. However, little is known about how the altered microbiota affect HNSCC pathogenesis or its
treatment. Currently, most studies linking the microbiome to cancer have focused on gut microbiota, which
either contributes locally to colorectal cancer pathogenesis, or more broadly, modulates metabolism and
immunity systemically. The oral cavity, which is more directly relevant to the local microenvironment in
HNSCC, harbors one of the most complex and diverse microbiomes of all human anatomical sub-sites.
However, how either the gut or oral microbiotas shape the local and systemic microenvironment in HNSCC
pathogenesis and treatment are completely unknown.
 Our long-term goal is to determine the functional role(s) and mechanisms of action of the microbiome in
HNSCC and to translate these findings into novel preventative and therapeutic strategies. Our central
hypothesis is that dysbiosis arising during HNSCC pathogenesis acts through Toll-like Receptor 2 signaling
pathways to accelerate tumor development and compromise response to therapies directed at the PI3 kinase
pathway, a key driver of HNSCC. This hypothesis has been formulated on the basis of publications and
preliminary data produced in the applicants' laboratories and will be tested by pursuing two specific aims that
will: 1) Test the hypothesis that TLR2 signaling mediates microbiome-related HNSCC pathogenesis and 2)
Test the hypothesis that dysbiosis-stimulated TLR2 signaling compromises anti-PI3K therapy. Our approach is
innovative because it represents a departure from the status quo by utilizing unique experimental mouse
models and state-of-art technologies to move beyond observational human studies to delineate the molecular,
cellular, and immunological mechanisms induced by the microbiome in HNSCC pathogenesis. The proposed
research is significant because it is expected to advance and expand understanding of how the microbiome as
a whole, as well as specific microbial species, impacts host immunity in HNSCC development and
immunotherapy. Ultimately, such knowledge has the potential to be developed into effective therapies for
HNSCC patients, a pressing need given the significant incidence and poor prognosis of this disease.

## Key facts

- **NIH application ID:** 10063370
- **Project number:** 1R21DE029262-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Daniel N Frank
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $233,250
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063370

## Citation

> US National Institutes of Health, RePORTER application 10063370, Oral Microbiota and Toll-Like Receptor Pathways in Head and Neck Cancer (1R21DE029262-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10063370. Licensed CC0.

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