# Improvement of cellular immunotherapy during dysbiosis - A. A. Brint Supplement

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2024 · $43,275

## Abstract

Project Summary
The use of antibiotics has significantly increased in recent years. Antibiotics (ABX) severely alter the gut
microbiome, destroying potentially pathogenic bacteria, as well as beneficial ones—producing a state of
microbial imbalance called dysbiosis. Notably, a diminished gut microbiome has severe defects on the immune
system, yet how these defects may affect cellular immunotherapy is largely unknown.
 To better understand how dysbiosis influences cellular immunotherapy, we focused on melanoma as an
exemplary immunogenic solid tumor. The incidence of melanoma has increased drastically over the past
decades, with its morbidity rate continuing to outpace that of most other cancers. Early stages of melanoma are
often successfully controlled and treated; yet patients with advanced stages of melanoma are treated with cellular
immunotherapy and only 50% respond. We hypothesize that ABX-induced dysbiosis dictates, at least in part,
the reduction in treatment efficacy.
 Our overall goal is to define the systemic effects of antibiotic-induced dysbiosis on the distal tumor
microenvironment and develop therapies to promote antitumor immunity. The major objective of this application
is to overcome dysbiosis-induced ICAM-1 suppression and thereby enhance the effectiveness of cellular
immunotherapy. Attaining this objective will be the next step in increasing the efficacy and response rate of
immunotherapies. We formulated a robust and unbiased approach using various melanoma models to
accomplish the following Aims:
Aim 1. Identify ABX primarily responsible for stromal immune suppression resulting in tumor progression.
Aim 2. Increase ICAM-1 on tumor-associated endothelial cells during dysbiosis.
Aim 3. Increase cellular immunotherapy efficacy in melanoma during dysbiosis.
 Completing these aims will expand our understanding on how antibiotics-induced perturbation of the gut
microbiome impacts the distal tumor microenvironment. This work has the potential to establish new paradigms
aimed at enhancing the efficacy and response rate of immunotherapies by modulating the tumor vasculature, as
all types of immunotherapy ultimately dependent on efficient trafficking of effector leukocytes into the tumor.

## Key facts

- **NIH application ID:** 10993899
- **Project number:** 3R01CA245083-03S1
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Ruud P.M. Dings
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $43,275
- **Award type:** 3
- **Project period:** 2024-03-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10993899

## Citation

> US National Institutes of Health, RePORTER application 10993899, Improvement of cellular immunotherapy during dysbiosis - A. A. Brint Supplement (3R01CA245083-03S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10993899. Licensed CC0.

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