Les Liaisons dangereuses: the tumour microenvironment, inflammation and the microbiota
Microbiota, systemic inflammation and the tumour microenvironment as parts of a single signalling network: the VITAM.BIO project funded by Fondazione Cariverona explores these "dangerous liaisons" across models of several cancers.
A single biological system
The project "Les Liaisons dangereuses: the tumour microenvironment, systemic inflammation and the microbiota," funded by Fondazione Cariverona under the 2022 Research and Development Call, was created to explore the interactions between the tumour microenvironment, systemic inflammation and the microbiota. These three components form a dynamic network of cellular, immune and metabolic signals that can influence the onset, progression and treatment response of several cancers. The work focuses in particular on models of oropharyngeal, colorectal, glial and melanoma tumours, aiming to identify new pathogenic mechanisms and possible therapeutic strategies.
The pathogenic triangle
The project's rationale is that the microbiota, systemic inflammation and the tumour microenvironment do not act as separate elements but as interconnected parts of a single system. The microbiota, when altered in its composition and function, can contribute to carcinogenesis through dysbiosis, modulating cellular metabolism, the immune response and the production of bioactive molecules. Systemic inflammation is the second key element: metabolites and signals of microbial origin can promote a chronic inflammatory state, increasing genomic instability and creating an environment favourable to tumour development. The tumour microenvironment, finally, integrates these signals and can favour the survival, proliferation and immune evasion of tumour cells, as well as resistance to therapies.
The microbiota, inflammation and the tumour microenvironment are not separate elements, but parts of a single signalling network.
Collaborations and new molecular targets
The work was enriched by exchanges with international partners. In particular, the collaboration with the group at Stanford University — through Dr Francesca Mengoni in the laboratory of Prof. Eugene Butcher — helped identify new molecular targets. Attention turned to the mechanisms of lymphocyte chemoaffinity and to the signals of immune trafficking toward non-intestinal mucosae and the central nervous system, as described in the study by Ocón et al. (2024).
Therapeutic prospects
Understanding these "dangerous liaisons" can open the way to integrative medicine strategies. Among the most promising is the targeted modulation of the microbiota — for example with personalised synbiotics — to restore microbial balance and positively influence the tumour microenvironment. Approaches of this kind could, in the future, improve the response to cancer therapies and help identify new biomarkers of disease progression.