The hidden players: The mycobiome of pancreatic ductal adenocarcinoma tumors

The microorganisms that inhabit the human body are known to play a role in human health and disease. Continuing to elucidate their specific role in disease progression is, however, necessary. The imbalance of these microorganisms-known as dysbiosis-has been linked to a myriad of intestinal diseases, and more recently to cancer. Despite making up less than 0.1 % of the human microbiome, dysbiosis of the fungal component of the microbiome-the mycobiome-has been found to contribute to the tumorigenesis and progression of certain types of tumors, pancreatic ductal adenocarcinoma (PDAC) included. The quantity and composition of the mycobiome was found to differ between healthy pancreatic tissue, the gut mycobiome of PDAC patients and PDAC tissue. Moreover, in a murine model of PDAC, it was shown that fungal ablation had a protective effect on tumor growth, and that specific fungal species, such as Malassezia globosa, contribute to tumor growth as well as to the inflammatory environment observed in PDAC tumors which promotes tumor progression. Research shows that fungal presence contributes to shaping the immune microenvironment through the activation of the complement system and/or by eliciting a type 2 immune response. Despite these preliminary findings, given the novelty of the field and of the bioinformatics pipelines used to analyze sequencing data, standardized approaches are still under development, thus leading to disagreement on the reliability of these results. The purpose of this review is to provide an up-to-date overview of the current research regarding the contribution of the fungal mycobiome in PDAC tumor progression and the overall tumor microenvironment (TME) of PDAC tumors.