# Translation of commensal bacteria mechanism for immunotherapy

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2021 · $196,992

## Abstract

PROJECT SUMMARY
Microbiota are associated with remarkable effects on host health and disease. Notably, discrete species of
commensal bacteria have been correlated with improved patient responses to cancer immunotherapy. However,
the molecular mechanisms underlying the functions of these beneficial bacteria remain poorly understood. In
particular, specific strains of Enterococci have been linked with improved response to anti-PD-1/PD-L1 treatment
in patients with metastatic melanoma, lung, and kidney cancers, but their mechanism of action has not been
elucidated nor employed to improve cancer immunotherapy. Recent work from the Hang laboratory has
demonstrated that these beneficial strains of Enterococci have unique peptidoglycan composition and
remodeling enzymes. Based on these studies, this project hypothesizes that specific strains of Enterococci may
prime innate immune signaling pathways and enhance anti-PD-1/PD-L1 immunotherapy against metastatic
cancers. To evaluate the activity and mechanism(s) of Enterococci during immunotherapy as well as co-opt their
protective factors for cancer immunotherapy, this proposal will examine how specific Enterococci strains alter
cancer growth, immune cell populations, and microbiota composition in mouse models of cancer immunotherapy.
In addition, the Hang laboratory will identify Enterococci protective factors and engineer them into existing human
probiotics to translate our basic microbiota-cancer immunotherapy findings into novel therapeutic agents. Finally,
the Hang laboratory will also synthesize novel immunomodulatory small molecules that activate host pathways
used by Enterococci to enhance cancer immunotherapy. These studies will reveal fundamental microbiota-
cancer immunotherapy mechanisms and develop new therapeutic strategies and agents to enhance cancer
immunotherapy.

## Key facts

- **NIH application ID:** 10064132
- **Project number:** 5R01CA245292-02
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Howard C Hang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $196,992
- **Award type:** 5
- **Project period:** 2019-12-02 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064132

## Citation

> US National Institutes of Health, RePORTER application 10064132, Translation of commensal bacteria mechanism for immunotherapy (5R01CA245292-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10064132. Licensed CC0.

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