# Improvement of cellular immunotherapy during dysbiosis- Resubmission

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2024 · $71,997

## Abstract

Summary/Abstract
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:** 11059705
- **Project number:** 3R01CA245083-04S1
- **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:** $71,997
- **Award type:** 3
- **Project period:** 2021-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11059705

## Citation

> US National Institutes of Health, RePORTER application 11059705, Improvement of cellular immunotherapy during dysbiosis- Resubmission (3R01CA245083-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11059705. Licensed CC0.

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