# (PQ10) The impact of the gut microbiome on the anti-tumor effects of radiotherapy

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $442,221

## Abstract

Abstract
The
and
functions,
pathophysiology
sheer enormity of the microbial biomass in the human intestinal tract, the co-evolution between humans
the microbiota, and the established function of the gut microbes in regulating normal host physiologic
are all consistent with the idea that alterations in gut microbial ecology play a role in the
of several conditions including cancer.Radiotherapy (RT) is an established curative and
palliative cancer treatment regimen, with approximately half of cancer patients with solid tumors receiving RT
some time during their disease. Mounting evidence also suggests that high-dose hypofractionated radiation
exerts potent immune modulatory effects, prompting immunological active tumor cell death inducing tumor
associated antigen (TAA) cross priming with elicitation of anti-tumor CD8+ T cells, and abscopal effects.
Although
cancer
whether
be
there have been groundbreaking responses to immunotherapy in certain malignancies such as lung
and melanomas, so far, immunotherapy is effective only in a portion of patients. This raises the issue of
there are additional important regulators of T cell function that are relevant to tumor control and could
harnessed to enhance radiotherapy.In support of this hypothesis, we have generated preliminary results
demonstrating that: a) Treatment with vancomycin
caused
a
significant
enhancement
of
the
tumor
inhibitory
effect vancomycin enhanced the ability of RT to increase ovalbumin specific and IFN-
producing CD8+ infiltrating T cells; c) gut gram+ depletion enhanced antigen presentation in the tumor
draining lymph nodes and e) the observed synergy between vancomycin and RT in eliciting an anti-tumor
immune response and inhibiting tumor growth was abrogated in IFN- KO animals or by CD8+ cell depletion.
Having established a direct link between the intestinal bacterial contents and radiotherapy, we propose the
following three specific aims:
Aim 1. To test whether the radiation enhancing effects of vancomycin are dependent on Gram+ bacteria, are
transferable to another host and to identify the bacterial species responsible;
Aim 2. To investigate the mechanism by which vancomycin treatment impacts both the priming and effector
phases of RT-elicited antitumor immune responses;
Aim 3. Perform a randomized pilot trial of antimicrobial therapy and stereotactic body radiation therapy in
early-stage non-small cell lung cancer.
Successful completion of these studies will firmly establish the microbiome as a target for therapeutic
intervention in patients receiving radiotherapy and will identify markers of response in the clinical setting.
of targeted radiation; b)

## Key facts

- **NIH application ID:** 10249985
- **Project number:** 5R01CA219871-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Andrea Facciabene
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $442,221
- **Award type:** 5
- **Project period:** 2018-08-10 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249985

## Citation

> US National Institutes of Health, RePORTER application 10249985, (PQ10) The impact of the gut microbiome on the anti-tumor effects of radiotherapy (5R01CA219871-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10249985. Licensed CC0.

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