Project description
The role of vitamin D in microbiome-mediated immunity
The gut microbiome plays a crucial role in regulating the immune system by maintaining a balanced interaction between commensal bacteria and the host, helping to prevent harmful inflammation. It also influences the development and function of immune cells, shaping responses to infections and maintaining immune tolerance. The ERC-funded MICROBIOGUARD project is focusing on the role of the microbiome in cancer immunity. A recent breakthrough revealed that vitamin D significantly boosts the gut microbiome's ability to drive T cell-mediated cancer immunity, impacting immunotherapy outcomes. The research team will investigate how vitamin D transforms microbial function and identify molecules capable of interacting with host cells to shape immunity and cancer onset.
Objective
Despite unprecedented clinical success, T cell-based immunotherapies present significant heterogeneity in response rates, often attributed to dampened activation and limited tumour infiltration of CD8+ T cells. Studies in mice and humans have shown that gut commensals can modulate anti-cancer immune responses dictating the efficacy of immunotherapy, but have failed to identify species that are consistently associated with improved patient prognosis.
I recently made a breakthrough in our efforts to understand the host determinants that define microbiome-dependent cancer immunity. I discovered that a single micronutrient, vitamin D (vitD), enhances the ability of the gut microbiome to induce potent T cell-mediated immunity to cancer, dictating immunotherapy success in pre-clinical models. Unlike any other study, I found that vitD modulates the function of the microbiome without significantly affecting its composition, diverging from a species-centric view of the microbiome to focusing on key host-microbiome interactions regulated by nutrient availability.
MICROBIOGUARD attempts to systematically dissect the multidirectional gut-immune-cancer axis. We first address a key question in the field: what defines a good microbiome that promotes immunity to cancer? Aim 1 of this proposal will dissect the mechanisms by which vitD transforms the function of the gut microbiome with a focus on identification of microbial-derived bioactive molecules. We will then assess how these altered microbial functions interact with host cells bidirectionally to shape anti-cancer immunity (Aims 1/2). We will broaden our findings and determine how vitD-microbiome-immune interactions impact cancer development. Finally, we will investigate if vitD enables human microbiome to augment immunotherapy response (Aim 3). Collectively, MICROBIOGUARD provides an unmatched opportunity to identify non-redundant microbiome-immune checkpoints that can be targeted to overcome immunotherapy resistance.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine immunology immunotherapy
- natural sciences biological sciences microbiology
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2024-STG
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M13 9PL Manchester
United Kingdom
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