Fig. 3

The tumor-associated-mycobiome mechanisms involved in triggering oncogenesis and cancer development. (a) Fungal-derived metabolites, such as aflatoxins and acetaldehyde, can directly damage DNA, hinder DNA repair, and induce epigenetic disorders, leading to gene mutations and carcinogenesis. (b) Fungi can exist in TME, interact with immune and cancer cells, and induce an immunosuppressive microenvironment. For example, pathogenic fungi A. fumigatus and C. albicans activate MDSCs function dependent on the Dectin-1/IL-1β signaling axis. MDSCs inhibit the activity of cytotoxic T lymphocytes and the accumulation of PD-1 CD8 T cells through multiple mechanisms. (c) Fungi are recognized by innate immune cells and induce cytokine production through the CARD9/NF-κB, CARD9/ERK, and Dectin-3/JAK-STAT pathways, leading to chronic inflammation and promoting tumor progression. (d) Fungi can also promote cancer progression through the complement system. For example, MBL binds Malassezia in pancreatic cancer to activate the complement cascade reaction. (e) Fungal metabolites, such as candidalysin, nitrosamines, and acetaldehyde, can trigger cancer cell invasion and metastasis. (f) Fungi can form biofilms on mucosal surfaces. (g) Bacteria and fungi can interact in several ways, including physical interactions by direct contact, chemical interactions, environmental modifications, metabolic by-products, and alterations in host responses