# Defining host-microbiota interactions during colorectal cancer and immune checkpoint blockade

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $237,724

## Abstract

PROJECT ABSTRACT
Immune checkpoint blockade has revolutionized the treatment of cancers and demonstrated sustained and
rapid efficacy in a number of patient populations. However, treatment outcomes can be variable across
individual cancer patients or specific tumor types. For example, most patients with colorectal cancer (CRC)
exhibit reduced efficacy to single agent checkpoint inhibitors. While this is partially accounted for by
segregating patients based upon mismatch repair status and tumor mutation load, the mechanistic
understanding of why most CRC patients do not respond to checkpoint blockade remains unclear. An
additional explanation for this variability stems from recent seminal studies demonstrating a significant role for
normally beneficial microbes, termed the microbiota, in controlling the efficacy of cancer checkpoint blockade
in humans and mice. Despite these advances, the mechanisms by which host-microbiota interactions modulate
anti-tumor immunity in the context of checkpoint blockade remains unclear, and the potential relevance of
these pathways to specific tumor types has not been examined. The fundamental goals of this high-
risk/high-reward proposal are to test a novel hypothesis that selective host-microbiota interactions
critically promote resistance to checkpoint inhibitors in CRC, and that targeting this pathway will boost
therapeutic responsiveness. We will comprehensively test this hypothesis using innovative patient samples
and powerful mouse models. Results from these studies could lead to the development of novel combinatorial
therapeutic approaches to boost the efficacy of cancer checkpoint inhibitors in multiple patient populations by
targeting host-microbiota interactions.

## Key facts

- **NIH application ID:** 10129923
- **Project number:** 5R21CA249274-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Gregory F Sonnenberg
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $237,724
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129923

## Citation

> US National Institutes of Health, RePORTER application 10129923, Defining host-microbiota interactions during colorectal cancer and immune checkpoint blockade (5R21CA249274-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10129923. Licensed CC0.

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