DIgesT

Disease progression can be controlled in cancer patients through the administration of immune checkpoint inhibitors (ICIs). But, ICIs
mainly show efficacy in subsets of patients and treatment costs are very high. Here, we use a dietary intervention to counteract
cancer-related immune suppression through interfering with metabolic pathways. DIgesT will enable the exciting possibility of
integrating cancer therapy with a dietary approach that is inherently low-risk and non-toxic, will encounter little regulatory barriers and
is highly cost-effective.
Given the effects of metabolic pathways on immune responses, we hypothesize that a fasting-mimicking diet (FMD) diet will reduce
proinflammatory and immunosuppressive responses, that are influenced by glucose and lipid metabolism, to restore effective
antitumor immunity.
DIgesT aims to:
-Determine if FMD modulates immune cell profiles in cancer patients and tilts the balance from immunosuppressive to antitumor
immune responses
-Evaluate in mouse models if FMD improves antitumor immune response, alone or combined with ICIs
-Clarify the molecular mechanisms underlying FMD-induced immune modifications
-Analyze the effect of FMD on gut microbiota, as a possible link to systemic immune modulation
Two parallel approaches will be used: 1) Investigating FMD immune effects on tumour immunity in clinical setting (breast cancer and
melanoma) and 2) Investigating FMD immune effects on tumour immununity in murine cancer models.
DIgesT results and expected impacts:
•Knowledge on the immune effects of FMD in preclinical and clinical settings
•Preclinical evidence of FMD potentiating effects on immunotherapy (ICIs)
•Improving cancer treatment strategies and survival rates, and quality of life
•Creating networking infrastructures and databases, international sharing of data and knowledge
•Streamlining research priorities and research needs at the EU level and beyond