The National Cancer Institute (NCI), part of the National Institutes of Health (NIH), has announced the reissuance of the funding opportunity titled *Modulating Human Microbiome Function to Enhance Immune Responses Against Cancer* (R01 Clinical Trial Not Allowed). This grant supports research focused on understanding how the human microbiome interacts with the immune system to either promote or inhibit cancer, with the ultimate goal of identifying novel molecular targets for cancer prevention. Specifically, the funding encourages studies that explore how specific microbes or their metabolites impact immune responses, preventing tumor formation or enhancing anti-tumor immunity.

Research proposals should aim to elucidate the mechanisms by which host-microbe interactions influence immune responses that are crucial to cancer prevention. This may include studying how beneficial microbes prevent tumor-associated inflammation, or how microbial metabolites influence the immune system’s ability to suppress or promote tumor formation. Applications are encouraged to address how different concentrations, timing, and durations of microbial administration affect their effectiveness. Preliminary data supporting the proposed research is required for submission to this opportunity, while a companion opportunity (PAR-22-062) supports exploratory or pilot projects.

Projects supported by this grant could include research that investigates how certain microbes inhibit cancer, how microbial metabolites affect immune functions, or how immune cells are modulated by microbial signals in cancer prevention. Specific areas of interest include understanding the role of gut microbiota in immune system development, immune responses related to chronic inflammation, and the role of the microbiome in modulating anti-tumor immune responses. Non-responsive applications include those that establish only a correlation between microbial species and tumor immunity without investigating mechanisms, or those focused on non-immune-related tumor pathways.

Applicants may request budgets that reflect the actual needs of their projects, with no specific budget cap. The maximum project period is five years. Eligible organizations include higher education institutions, nonprofits, government entities, small businesses, and foreign institutions. All applicants must complete necessary registrations in systems such as SAM, Grants.gov, and eRA Commons prior to submission.

This funding opportunity is highly competitive and subject to NIH peer review. Evaluation criteria include the significance of the research, the strength of the investigative team, the innovation of the approach, and the project's potential to impact cancer prevention strategies. Researchers are encouraged to incorporate state-of-the-art methods such as bioinformatics, metabolomics, and molecular immunology to identify the complex interactions between host immune systems and the microbiome that may modulate cancer risk.

Key application deadlines occur multiple times annually, with the earliest submission date of January 5, 2022, and standard NIH due dates continuing until January 8, 2025. For those applying for $500,000 or more in direct costs, applicants must contact NCI program staff at least six weeks before submission. All applications must be submitted electronically, and successful applicants will receive formal Notices of Award (NoA) via email. Compliance with NIH data management and sharing policies is required for all funded projects.

For further inquiries, researchers are encouraged to contact NCI scientific or grants management officials.