# The impact of genetic diversity among Akkermansia strains on the effectivenes of immune checkpoint inhibitors in cancer immunotherapies

> **NIH NIH R21** · DUKE UNIVERSITY · 2020 · $188,169

## Abstract

ABSTRACT:
Microbes in the gastrointestinal tract (GI) play a critical role in maintaining the metabolic
and immunological health of their human hosts. The impact of the microbiota on local
and systemic immunity is being increasingly recognized as an important modifier of the
success of immunotherapies, including those directed against cancers. For instance,
germ free animals colonized with microbiotas derived from cancer patients that
responded (responders - R) to immune checkpoint inhibitors (ICI) displayed enhanced
clearance of tumors upon ICI therapy as compared to animal colonized with microbiotas
derived from patients that did not respond (non responders - NR). One of the organisms
that is consistently associated with R patients is the obligate anaerobic bacterium
Akkermansia muciniphila, which may contribute to dampening mucosal inflammation
and regulating systemic immunity. Importantly for cancer immunotherapy, administration
of A. muciniphila is sufficient to enhance the effectiveness of ICIs in mouse models of
renal cell carcinomas (RCC) and non-small cell lung cancers. We propose to survey the
diversity of clinical A. muciniphila isolates in two unique patient populations (one
focused on cancer and one on metabolic disease), test their impact in mouse models of
cancer immunotherapy, and apply new tools in Akkermansia molecular genetics to
define the contribution of various A. muciniphila factor(s) on successful anti-tumor
therapy.
We expect that by the end of this study that we will have identified strains with the
greatest potential for use as “adjuvants” of ICI and defined the genetic basis of some of
the traits responsible for their enhanced activities. Given the current commercial interest
on Akkermansia as a probiotic, we envision a relatively rapid path from strain
identification and/or engineering to a biological that can be fast-tracked for clinical use.

## Key facts

- **NIH application ID:** 9952829
- **Project number:** 1R21CA249243-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** You-Wen He
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $188,169
- **Award type:** 1
- **Project period:** 2020-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952829

## Citation

> US National Institutes of Health, RePORTER application 9952829, The impact of genetic diversity among Akkermansia strains on the effectivenes of immune checkpoint inhibitors in cancer immunotherapies (1R21CA249243-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9952829. Licensed CC0.

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