# Microbiota-mediated enhancement of the anti-tumor effect of natural killer cells

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2023 · $174,670

## Abstract

PROJECT SUMMARY/ABSTRACT
 Pancreatic ductal adenocarcinoma (PDAC) is now the 3rd leading cause of cancer related death in the
United States. The overwhelming majority of patients receive systemic chemotherapy as part of a neoadjuvant,
adjuvant, or palliative treatment regimen. These systemic agents do not provide durable survival benefits in
patients with PDAC. The reason for this is unknown and given that there are no promising new agents on the
horizon, novel strategies to increase treatment responsiveness or identify preventative measures are desperately
needed. Our group and others have reported the importance of the host microbiome on PDAC development and
progression. The microbiome is the milieu of microorganisms that share the body space of every individual and
has been increasingly associated with a variety of human diseases, including pancreatic cancer. Building on
prior published work and provocative preliminary data from our lab, we propose novel experiments that will
identify bacteria as modulators of NK cells and their anti-tumor function in order to augment response to
chemotherapy and provide a preventative and treatment strategy. Our innovative approach utilizing gnotobiotic
technology, microbial manipulation, and the innate immune system to enhance PDAC responsiveness to
chemotherapy has not been undertaken previously and will advance the field of pancreatic cancer research.
 We hypothesize that selective intestinal bacteria can delay or prevent PDAC development and
furthermore, enhance the anti-tumor efficacy of gemcitabine and 5-FU, common chemotherapeutic agents used
to treat PDAC. In order to test this hypothesis, we propose the following specific aims:
Aim 1: Establish the ability of E. hirae to prevent PDAC development utilizing a xenograft and genetic
mouse model of pancreatic cancer.
Aim 2: Establish the impact of E. hirae to augment chemotherapy efficacy in PDAC.
 With fulfillment of the Specific Aims, this proposal will confirm the role of Enterococcus hirae to enhance
the anti-PDAC role of NK cells in PDAC prevention as well as its response to chemotherapy treatment. Such
knowledge will advance our understanding of host factors that impact the responsiveness of PDAC to
chemotherapy and provide transformative data to support a National Institutes of Health R01 application and
first-in-human trials for bacterial manipulation with E. hirae that targets the anti-PDAC role of NK cells as a
preventative and treatment strategy.

## Key facts

- **NIH application ID:** 10654555
- **Project number:** 5R21CA263462-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Christian Jobin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $174,670
- **Award type:** 5
- **Project period:** 2022-07-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10654555

## Citation

> US National Institutes of Health, RePORTER application 10654555, Microbiota-mediated enhancement of the anti-tumor effect of natural killer cells (5R21CA263462-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10654555. Licensed CC0.

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