Intra-tumoural microenvironment and bugs-based drug design: foreseeable future in oncology and immuno-oncology

The term tumour microenvironment (TME) encompasses the coexistence of microorganisms and different cellular elements including endothelial cells, macrophages, cancer-associated fibroblasts and a complex network of microvessels. Integration of tumour immunity and intratumoural microbiome into anti-cancer strategies represents a promising frontier in precision oncology (for instance in case of solid cancers, such as pancreatic or colorectal tumours). Characterization of the intratumoural microbial signature has emerged as a critical step in drug discovery, influencing therapeutic efficacy as well as resistance. There are several approaches, such as elimination of pathogenic microorganisms within the TME, modulation of specific microbial-immune axes, including interactions among microbial species that may enhance or suppress tumour progression, and exploitation of bacterial strains engineered to express pro-drug-converting enzymes for localized tumour therapy via intratumoural injection. Furthermore, tumour organoid-immune co-culture models, particularly when combined with 3D bioprinting technologies, offer robust experimental platforms for dissecting tumour-microbiome-immune crosstalk. The reciprocal communication between the immune system and the tumour-associated microbiome/metabolome highlights novel opportunities for therapeutic innovation in oncology and immuno-oncology.