In pancreatic ductal adenocarcinoma (PDA), the abnormal colonization of fungal communities has become a research hotspot. Compared to normal tissue, the abundance of fungi in tumor tissues of PDA patients increased by up to 3000 times, with the enrichment of Malassezia being particularly significant. These fungi activate the host complement system (such as the MBL-C3 pathway), triggering local inflammatory responses and promoting tumor growth. This indicates that Malassezia is not only a "marker" in the tumor microenvironment but also a potential driver of cancer development.
Researchers have revealed several mechanisms by which fungi "manipulate" the course of tumors.
The researchers also discussed the relationship between fungi and therapeutic responses, emphasizing that fungi can not only serve as diagnostic markers but also as intervention targets with dual potential. Studies have shown that 13 fungi in stool can be used as biomarkers of colorectal cancer, and their abundance changes are highly correlated with non-invasive diagnosis. Aspergillus ( Aspergillus sydowii ) detected in lung cancer tissues is associated with immunosuppressive microenvironment, suggesting that it may be an independent risk factor for prognosis. Fungi can affect the efficacy of chemotherapy and radiotherapy. For example, symbiotic fungi regulate the immune response in the tumor microenvironment by regulating the function of dendritic cells and myeloid cells, thus enhancing the sensitivity of radiotherapy. Melanoma studies have shown that the amount of fungi in the tumor is associated with the efficacy of PD-1 inhibitors, and that fungal communities may indirectly affect treatment responses by remodeling the immune microenvironment. In view of the mechanism of fungal carcinogenesis, the team proposed multiple intervention ideas: inhibiting fungal virulence factors (such as candidalysin), targeting complement activation pathways (such as MBL/C3aR blockers), or regulating fungal-bacterial interaction networks (such as microbiota transplantation).
The research team calls for enhanced interdisciplinary collaboration in microbiology, oncology, and immunology to accelerate breakthroughs from the laboratory to clinical settings. The "dual role" of fungi in the tumor microenvironment (cancer promotion and potential therapeutic targets) is gradually being unraveled. With technological advancements and innovations across multiple fields, it may be possible in the future to achieve early cancer detection, improved efficacy, and prevention of recurrence by modulating the fungal community, injecting new vitality into global cancer efforts.
Cancer Biology & Medicine
10.20892/j.issn.2095-3941.2024.0240
Tumor-related fungi and crosstalk with gut fungi in the tumor microenvironment
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