Iliyan D. Iliev, PhD, CRI Lloyd J. Old STAR Weill Cornell Medicine Area of Research: All Cancers Cancer is among the leading causes of death worldwide and host-bacterial microbiota immune 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. Upon providing the first evidence for the role of gut mycobiota in inflammation, Dr. Iliev and colleagues have defined central mechanisms of mycobiota interactions with host immunity and neurons, and determined fungal toxins and metabolites with potent impact on the host. In this proposal, Dr. Iliev presents compelling evidence for the presence of live, metabolically active mycobiota in human tumors and experimental data that support a novel hypothesis: fungi play an important role in cancer growth and response to checkpoint inhibitor immunotherapy through the interaction of fungal metabolites with the immune system and with bacteria. With this “high-risk high-reward” proposal Dr. Iliev will investigate how fungi, their metabolites and toxins influence tumor growth, progression, and response to immunotherapies. He will further determine how fungal genetic variants, called strains, that vary between patients and tumor types influence these processes directly or through “transkingdom” interaction with bacteria in tumors. He will use novel methodology allowing for the detection and characterization of fungi in tumors and in patient’s blood to determine utility of the mycobiome and “circulating” fungal DNA as a predictor of cancer progression, survival, and response to immunotherapies. Furthermore, he will determine specific immune mediators and cells of the immune system that interact with fungi in the tumors and target these cells or fungi directly, to delay tumor growth and restore the response to antitumor immunotherapies. The results of these studies will contribute towards a better understanding of host-mycobiome immune interactions in cancer and aim to provide a basis for novel diagnostic, therapeutic and co-therapeutic anticancer approaches by targeting the fungal arm of the microbiome. Projects and Grants Immune interactions with fungal microbiota during cancer progression and immunotherapy Weill Cornell Medicine | All Cancers | 2022
