Description

This NIH Funding Opportunity Announcement (FOA) aims to support exploratory and developmental basic research projects that investigate the mechanisms by which the human microbiome either inhibits or enhances anti-tumor immune responses. The goal is to identify novel molecular targets that can be leveraged for cancer prevention strategies.

Research should focus on how host interactions with specific microbes or microbial consortia, as well as their metabolites, influence immune responses that either promote or prevent inflammation-associated or sporadic tumor formation. The effectiveness of beneficial microbes may depend on factors such as their concentration, timing, and duration of administration, which must be rigorously studied.

The FOA encourages innovative, novel projects that break new ground or extend previous discoveries in new directions. It is intended for pilot or exploratory studies; a companion FOA (PAR-22-061) supports more developed projects with preliminary data.

Scientific Context

• The gut microbiome plays a critical role in cancer etiology and prevention by affecting epithelial barrier integrity, modulating chronic inflammation, and influencing innate and adaptive anti-tumor immunity.
• The "immuno-oncology-microbiome axis" describes these host-microbe interactions.
• Altering the microbiota through beneficial microbes or inhibiting tumor-promoting microbes has shown promise in animal models for preventing inflammation-associated and sporadic cancers.
• The immunomodulatory effects of microbiota are often species- and strain-specific, requiring precise understanding of host-microbe signaling pathways.
• There is a significant knowledge gap in the molecular mechanisms and signaling pathways mediating these effects, highlighting the need for basic research.
• State-of-the-art techniques such as metabolomics, molecular immunology, bioinformatics, and cancer models should be integrated to establish physiological roles of commensal microbes in tumor immunology.
• Computational approaches can help identify microbial and immunological patterns that serve as molecular fingerprints of cancer risk.

Examples of Appropriate Research Topics

• Investigating how Lactobacilli species inhibit colon cancer and the role of T-cell-dependent IgAs in this process.
• Examining the influence of commensal microbiota on differentiation of naïve T cells into Th17 subsets that may suppress or promote tumor formation.
• Evaluating the role of colonic Foxp3+RORγt+ regulatory T cells in mediating anti-inflammatory effects of commensal microbes to prevent colon cancer.
• Studying how modulation of commensal hydrogen sulfide (H2S) production affects host immunosurveillance.
• Assessing the impact of short-chain fatty acid (SCFA) production on anti-tumor immune functions of tumor-associated macrophages.
• Exploring how microbial bile acid metabolism influences immune responses in liver and colon tumors.

Non-Responsive Applications

Applications will be excluded if they:

• Only establish associations between microbial species and tumor immunity without defining or testing mechanisms.
• Focus on microbial modulation of non-immune tumor stroma signaling.
• Focus on microbial mechanisms that do not modulate tumor immunity.