The role of the mycobiome in cancer

Abstract Cancer is among the leading causes of death worldwide and host-bacterial microbiota interactions profoundly influence tumorigenesis, cancer progression and response to therapies. Nevertheless, the role of fungi (mycobiota) in these processes remain largely unexplored, missing a potential opportunity for developing novel diagnostic, preventative, and therapeutic strategies. Across the population, colorectal cancer (CRC) is the third most common cancer type. In addition to bacteria, we recently described the presence of live, transcriptionally active fungi in colorectal cancers. Here, we preset further evidence for the presence of active mycobiota in colorectal tumors and experimental data supporting a hypothesis that fungi play an important role in colon cancer growth and response to therapies through the interaction of fungal metabolites and virulence factors in the tumor macro- and micro-environment. We will use novel methodologies and in vivo modeling allowing to determine fungal species and factors that influence CRC. We will determine specific immune mediators and cells of the immune system that interact with fungi in the tumors, and pinpoint mechanisms by which specific fungal strains influence the tumor microenvironment and impact tumor growth. We will further characterize fungi in tumors of patient and mice to determine the utility of the mycobiome as a predictor of cancer progression, survival, and response to therapies. The results of these studies will contribute towards better understanding of host-mycobiota interactions in cancer and might provide a basis for novel diagnostic, therapeutic and co-therapeutic anticancer approaches in CRC by targeting the fungal arm of the microbiome.