# Small extracellular vesicles as biomarkers of prognosis and response to therapy in head and neck cancer

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $686,036

## Abstract

PROJECT SUMMARY/ABSTRACT
Biomarkers that reliably inform the selection of therapy or prognosis for patients with head and neck squamous
cell carcinoma (HNSCC) are lacking. This can result in the use of overly aggressive or ineffective therapy with
the associated negative impact on quality of life and mortality. Thus, there is a great need for the development
of non-invasive biomarkers that accurately predict response to therapy or prognosis of HNSCC. Emerging data
suggest that analysis of the cargos of small (30-150 nm) extracellular vesicles (sEV), also known as exosomes,
in body fluids is a promising approach to the detection of non-invasive biomarkers in cancer, including HNSCC.
In cancer patients, plasma sEV are mixtures of tumor-derived exosomes (TEX) and vesicles produced by non-
malignant cells (NTEX) such as leukocytes. We found that TEX are a prominent but variable subset of sEV in
HNSCC patients’ plasma. TEX recapitulate the content of tumor cells, while the molecular cargo of NTEX
resembles that of non-malignant leukocytes, largely T cells, reprogrammed by TEX. Our data indicate that both
these sEV subsets mediate immune suppression and influence responses to therapy. We hypothesize that in
HNSCC patients, TEX as well as NTEX mediate immune suppression and are responsible for poor prognosis
and resistance to anti-cancer therapies. Using a novel immune capture-based technology, we will separate TEX
from NTEX in HNSCC patients’ plasma and will then simultaneously evaluate these two sEV subsets as potential
biomarkers. In Aim 1, we will establish efficacy of the immune capture strategy for TEX and NTEX isolation from
HNSCC patients’ plasma and determine the potential of these sEV subsets to serve as biomarkers of cancer
and immune competence, respectively. Levels as well as phenotypic profiles and immunosuppressive functions
of the two sEV subsets will be evaluated and assessed for their ability to discriminate HNSCC patients from
healthy donors (HDs). In addition, high-resolution (HR) LC-MS/MS will be used to identify proteins in TEX and
NTEX that could be utilized as prognostic or predictive biomarkers. In Aim 2, we will evaluate the utility of TEX
and NTEX as biomarkers of prognosis in patients with locally advanced HNSCC treated with standard of care
therapy (N=200). Utilizing TEX and NTEX isolated from well-annotated existing pre-treatment plasma samples,
nanoflow cytometry, functional assays, and targeted HR LC-MS/MS will be used to assess phenotypic profiles
and immunosuppressive functions. We will correlate TEX and NTEX plasma levels and profiles with clinical
endpoints. In Aim 3, we will investigate the utility of TEX and NTEX as biomarkers of response to anti-PD-1 mAb
immunotherapy in HNSCC patients diagnosed with recurrent/metastatic disease (N=80). TEX and NTEX
characteristics will be assessed as in Aim 2, and we will evaluate whether they are predictive of the efficacy of
anti-PD-1 mAb therapy. The simultaneous assessment of ...

## Key facts

- **NIH application ID:** 10802423
- **Project number:** 5R01DE031299-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Brenda B. Diergaarde
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $686,036
- **Award type:** 5
- **Project period:** 2023-03-15 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802423

## Citation

> US National Institutes of Health, RePORTER application 10802423, Small extracellular vesicles as biomarkers of prognosis and response to therapy in head and neck cancer (5R01DE031299-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10802423. Licensed CC0.

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