The human body is an ecosystem, home to trillions of microorganisms collectively known as the microbiome. While scientific attention historically focused on bacteria, recent research has shifted to the mycobiome, the community of fungi that coexist within us. This fungal population, though less abundant than bacteria, is proving to be an active player in human health and disease. The connection between fungi and cancer is a rapidly expanding area of study, challenging previous assumptions about tumor biology. This new understanding suggests that fungi actively participate in the development and progression of various cancers.
The Intratumoral Mycobiome: Where Fungi Reside
The physical presence of fungal species directly within tumor tissue defines the intratumoral mycobiome. Scientists confirm these fungi are not environmental contaminants but metabolically active components of the tumor microenvironment. The discovery of fungal DNA and living fungal cells inside cancer masses across a wide range of human cancers, including breast, colon, and lung, highlights this unexpected residence. Researchers are still investigating how fungi migrate to and colonize tumors throughout the body.
Analysis of these tumor-resident fungi reveals certain genera are frequently implicated in specific cancer types. Candida species are often found in gastrointestinal cancers, while Malassezia species show enrichment in pancreatic and colorectal tumors. Aspergillus species have been associated with lung tumors, suggesting a site-specific fungal signature for different malignancies. These fungal communities are often in a state of dysbiosis, an imbalance compared to healthy tissue, which may influence disease.
How Fungi Drive Cancer Progression
Fungi influence cancer progression through several biological mechanisms, impacting the tumor’s environment and the host’s genetic material. One direct mechanism involves the production of mycotoxins, which are potent fungal toxins. A classic example is aflatoxin, produced by certain Aspergillus species, which is a known carcinogen capable of causing DNA damage and driving liver cancer development. Other fungal metabolites, such as candidalysin from Candida species, are also believed to exert genotoxic effects that contribute to oncogenesis.
The continuous presence of fungi can trigger chronic inflammation, a known promoter of tumor growth. Fungi interact with immune cells, activating pathways that lead to the persistent release of pro-inflammatory molecules like IL-1β. This sustained inflammatory environment alters the tumor microenvironment, making it more conducive to cell proliferation and survival.
Fungi further drive progression by modulating the host’s immune response, often suppressing the body’s ability to fight the tumor. They interact with immune cells like macrophages and T-cells, creating an immunosuppressive environment that shelters cancer cells from destruction. For instance, certain fungi can induce the exhaustion of CD8+ T cells, the primary anti-tumor immune cells, making the immune response less effective.
Fungal Influence on Diagnosis and Treatment Outcomes
The specific composition of the mycobiome is emerging as a potential tool for clinical application in predicting disease course and treatment response. Mycobiota profiles can serve as diagnostic and prognostic biomarkers, offering clues about disease severity and recurrence. For example, the presence of Aspergillus tanneri in renal cell carcinoma correlates with a worse prognosis for patients. Similarly, high fungal diversity in some tumors has been associated with less favorable outcomes, suggesting an aggressive disease marker.
Fungi also play a significant role in modulating the effectiveness of cancer therapies. Certain fungal species or their metabolites can promote resistance to chemotherapy, reducing the benefit of standard treatments. The interplay between fungi and the immune system is particularly relevant for immunotherapy, which harnesses the body’s immune cells to attack tumors. Fungal communities can alter the tumor microenvironment in ways that counteract the intended effect of these drugs, leading to poor response rates. Understanding these interactions may lead to strategies where antifungal agents are used alongside conventional cancer treatments.
Fungi as a Source of Anti-Cancer Therapies
While some fungi pose a risk in cancer progression, the fungal kingdom is also a source of compounds with tumor-fighting potential. Fungi, particularly endophytic fungi that live inside plants, are prolific producers of bioactive metabolites. These compounds are part of the fungi’s natural defense mechanism, and many possess properties valuable in oncology.
One well-known example is Taxol (paclitaxel), an anti-cancer drug originally isolated from the Pacific yew tree. Scientists later discovered that the endophytic fungus Taxomyces andreanae, which lives symbiotically within the yew tree, also produces the same complex molecule. This finding demonstrated that fungi could be a more sustainable and scalable source for this potent chemotherapy agent. Beyond Taxol, other fungal-derived substances, such as polysaccharopeptides from medicinal mushrooms like Coriolus versicolor, are being researched for their ability to modulate the immune system and inhibit tumor growth. These metabolites represent a promising avenue for developing new drugs that can inhibit tumor proliferation or selectively induce cancer cell death.