# Colorado Head and Neck Cancer SPORE

> **NIH NIH P50** · UNIVERSITY OF COLORADO DENVER · 2024 · $46,330

## Abstract

ABSTRACT
This proposal is being submitted in response to PA-23-189 to support minority graduate student Anastasia
Abello. She is conducting work closely related to Dr. Xiao-Jing Wang’s project 2 of the CO HNC SPORE
CA261605
Head and Neck Squamous Cell Carcinoma (HNSCC) is associated with significant morbidity and mortality, with
immune checkpoint inhibitors (ICIs) showing limited efficacy. Emerging evidence suggests the potential impact
of altered microbiomes on cancer progression and immunotherapy response. Additionally, bacteria have been
detected inside tumors, including HNSCC. Recent studies suggest a crucial role of the oral microbiome in
modulating the efficacy of ICIs. Moreover, environmental factors, particularly diet, have been linked to
microbiome alterations and impaired immunotherapy response. I propose to use preclinical mouse models,
human clinical specimens, and multiple omics techniques to identify the mechanisms through which the oral
microbiome influences cancer progression and immunotherapeutic responses. This research aligns with the
parental SPORE project of improving immunotherapy, yet brings new studies addressing microbiome effects
on cancer therapeutics and holds promise for improving patient quality of life through better treatment
outcome. Overall, the goal of this proposal is to leverage unique murine models and human patient samples
to advance our understanding of the role of the oral microbiome in HNSCC and enhance therapeutic
approaches. The hypothesis of this proposal is that alterations to the oral microbiome through diet
significantly impact immunotherapeutic response in HNSCC via the mechanisms of direct interactions between
microbiomes, tumor cells, the microenvironment, and indirectly by inducing metabolic changes to the host and
microbial metabolites. Aim 1 will examine the effects of changes in the oral microbiome from a Western diet
(WD) and on tumor growth of mouse HNSCC models. Aim 2 will assess the role of the oral microbiome on
immunotherapy response upon changes from a WD in HNSCC mouse models. Additionally, this aim will
examine if there are differences in oral microbiomes of human HNSCC patients between immunotherapeutic
responder (R) and non-responder (NR). Aim 3 will identify spatial and systemic predictive marker candidates of
immunotherapy response affected by dietary-associated microbiomes in mouse HNSCC models and human
specimens. This study will provide insight into the interplay between the oral microbiome, diet, cancer
progression, and immunotherapy response. It will also identify predictive biomarkers linked to altered
microbiomes in HNSCC.

## Key facts

- **NIH application ID:** 10942730
- **Project number:** 3P50CA261605-03S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Antonio Jimeno
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $46,330
- **Award type:** 3
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10942730

## Citation

> US National Institutes of Health, RePORTER application 10942730, Colorado Head and Neck Cancer SPORE (3P50CA261605-03S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10942730. Licensed CC0.

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