# (PQ10) Enhancing responses to immune checkpoint blockade in melanoma via modulation of the microbiome

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $456,293

## Abstract

ABSTRACT
Melanoma is a major world health problem with an incidence rate that is rising rapidly. Within the past several
years, there has been tremendous progress in novel melanoma therapies – particularly with regard to
immunotherapy as highlighted by the FDA approval of ipilimumab (anti-CTLA-4 antibody) in 2011 and
pembrolizumab and nivolumab (anti-PD-1 antibodies) for melanoma in 2014 and 2015. Furthermore, when
CTLA-4 and PD-1 blockade are combined, response rates are significantly increased, leading to the FDA
approval of this regimen (ipilimumab + nivolumab) in 2015 – however, toxicity is admittedly high. Despite these
advances, there are still a significant proportion of patients who do not achieve clinical response to these agents.
Therefore, there is tremendous need to identify biomarkers that may predict response or resistance to immune
checkpoint blockade – either as monotherapy or in combination – and to identify actionable strategies that will
enhance the effectiveness of these potent therapies. Our group has been actively engaged in efforts to better
understand responses to immune checkpoint blockade therapies. In these studies, we performed deep immune
and molecular profiling in a cohort of patients on immune checkpoint blockade, and recently demonstrated that
an immune infiltrate in early on-treatment tumor biopsies is highly predictive of response. However it remains
unclear what contributes to enhanced responses, and there is a critical need to identify actionable strategies to
improve responses to therapy in all patients.
There is a growing appreciation of the role of the gut microbiome in shaping immune responses in health and
disease, and pre-clinical evidence that bacteria present within the gut may modulate differential responses to
immune checkpoint blockade in melanoma, though this concept has not been studied in patients. This represents
a significant knowledge gap, and insights gained could lead to therapeutic strategies to enhance responses to
immune checkpoint blockade in melanoma.
We have begun to address this knowledge gap in clinical samples from melanoma patients treated with immune
checkpoint blockade, and are also studying this in a murine melanoma model. We have preliminary evidence
suggesting that differential signatures exist in responders versus non-responders to therapy, and have insight
into mechanisms via immune profiling and metabolomic studies. We have also generated data in a murine
melanoma model, demonstrating differential tumor growth in C57BL/6 mice with identical genomes but differing
gut microbiomes. We will now build on these studies through this proposal to explore the role of the microbiome
in shaping anti-tumor immune responses and clinical responses to immune checkpoint blockade in melanoma.

## Key facts

- **NIH application ID:** 9997795
- **Project number:** 5R01CA219896-03
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Jennifer A. Wargo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $456,293
- **Award type:** 5
- **Project period:** 2018-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997795

## Citation

> US National Institutes of Health, RePORTER application 9997795, (PQ10) Enhancing responses to immune checkpoint blockade in melanoma via modulation of the microbiome (5R01CA219896-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9997795. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*