# Project 1

> **NIH NIH P50** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $280,877

## Abstract

PROJECT 1 SUMMARY
We hypothesize that interplay between host immune responses and the gut microbiota affect the efficacy and
toxicity of immune checkpoint inhibition (ICI) in melanoma patients. Increasing evidence suggests that gut
microbiota play important roles in regulating the innate and adaptive immune response to cancer
immunotherapy. We and others have provided compelling evidence that the gut microbiome is associated with
the efficacy and the toxicity of immunotherapy. We also showed that novel baseline pre-treatment T-cell
phenotypes and the levels and suppressive function of T regulatory cells in the peripheral blood were associated
with increased relapse-free survival (RFS) after PD-1 blockade in melanoma. Moreover, we found that alterations
in serum protein immune pathways were associated with decreased survival with PD-1 blockade, underlining
the importance of host immune responses for immunotherapy outcomes. Nonetheless, no definitive, large scale
human studies have identified the gut microbial taxa associated with the efficacy and/or toxicity of
immunotherapy, nor investigated their relationships with host immune responses.
The goal of Project 1 is to identify microbial and host immune biomarkers that predict the efficacy and toxicity of
ICI in a randomized phase III adjuvant trial testing combination PD-1/CTLA-4 blockade versus PD-1 alone in
patients with high-risk resected stage IIIB/C and IV melanoma. As part of a large, well-controlled randomized
and blinded trial (n=2000; a subset of n=1500 available blood/stool samples), we will evaluate gut microbiota in
stool and a series of innovative biomarkers in serum and peripheral blood immune cells, and examine the utility
of these biomarkers to predict clinical efficacy and toxicity from immunotherapy (Aims 1 and 2). Based on
integration of these biomarkers, we will additionally define cohorts of patients who may derive differential benefit
from combination versus single-agent checkpoint blockade (Aim 3). This study, based on a large clinical trial with
standardized treatments and clinical outcome as well as toxicity assessments, will provide excellent power for
biomarker identification with rigorous replications.
This research will improve patient care by defining predictive biomarkers and developing a predictive classifier
– using easily obtainable stool, serum, and blood samples – that can facilitate personalized immunotherapy
decisions. Finally, given the modifiable nature of gut bacteria, findings could lead to tailored microbe-targeted
interventional approaches to improve the efficacy of, and attenuate the toxicity of, ICI.

## Key facts

- **NIH application ID:** 10200701
- **Project number:** 5P50CA225450-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Jiyoung Ahn
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $280,877
- **Award type:** 5
- **Project period:** 2019-07-19 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200701

## Citation

> US National Institutes of Health, RePORTER application 10200701, Project 1 (5P50CA225450-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200701. Licensed CC0.

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