

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.
- Immune Regulation: Certain fungi (such as Candida albicans) are recognized by macrophages, which enhance glucose metabolism through the HIF-1 pathway, stimulate IL-7 secretion, and subsequently activate innate lymphoid cells (ILC3) to produce the oncogene IL-22.
- Signal Pathway Interference: The toxin candidalysin secreted by Candida can bind to the EGFR receptor, activating the MAPK signaling pathway and promoting the expression of cell proliferation-related factors (such as IL-1, G-CSF). Additionally, it can disrupt the function of tumor suppressor genes through the Wnt/β-catenin pathway.
- Fungal-Bacterial Synergistic Effect: In colorectal cancer, Candida forms positive correlation communities with specific bacteria (such as Dialister), exacerbating gut microbiota imbalance, while certain probiotics (such as Ruminococcus) are suppressed, collectively driving tumor progression.
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.
Original Publication
Authors: Yue Wang, Yiwen Wang, Yuhang Zhou, Yun Feng, Tao Sun and Junnan Xu.
Journal: Cancer Biology & Medicine
DOI: 10.20892/j.issn.2095-3941.2024.0240
Article Title: Tumor-related fungi and crosstalk with gut fungi in the tumor microenvironment
Article Publication Date: 15-Apr-2025
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Frequently Asked Questions
What role does *Malassezia* play in pancreatic cancer?
*Malassezia* fungi can significantly increase in tumor tissues and may trigger inflammatory responses that promote tumor growth, indicating their potential as both markers and drivers of pancreatic ductal adenocarcinoma.
How does candidalysin affect tumor growth?
The toxin candidalysin from *Candida* can activate the MAPK signaling pathway by binding to the EGFR receptor, leading to enhanced cell proliferation and potentially disrupting tumor suppressor functions.
What is microbiota transplantation and how can it help in cancer treatment?
Microbiota transplantation involves transferring beneficial gut bacteria from a healthy individual to a cancer patient, which may help restore microbiota balance and enhance the effectiveness of cancer therapies, potentially improving patient outcomes.
Source: EurekAlert!