There are hidden fungi in tumor cells

If, as William Paley thought and creationists maintain, there is an all-powerful creator, there is no doubt about one thing: he likes mushrooms. In kingdom Fungi, the kingdom of fungi, 150,000 species have been described, though mycologists say there are a few million more to discover. Fungi thrive in every conceivable environment, including tumor cells.

A microbiome is the community of microorganisms that can be found coexisting in an environment defined as the “theater of operations”. From this it can be deduced that the human microbiome is the set of all microorganisms (bacteria, fungi, viruses, protozoa and parasites) that live naturally inside our body, in addition to their genes and metabolites. It should not be confused with the term microbiota, which refers exclusively to living microorganisms residing in a given ecological niche.

The term microbiome contains both the microbiota (community of microorganisms) and their theater of activity (structural elements, metabolites, signal molecules, and surrounding environmental conditions). Modified from Berg et al. (2020).

There is a microbiome beyond bacteria

Today it is firmly established that the human microbiome prevents metabolic deficits, protects us from invading pathogens and maintains immune homeostasis. But still influenced by the bacteriological works of Robert Koch on the origin of infectious diseases, research in medical microbiology has always focused on our endosymbiotic bacteria, that is, on the bacteriome, which constitutes more than 99% of our microbiome.

However, the results of several recent clinical investigations have highlighted that the mycobiome, that is, the community of commensal fungi in and on an organism, coexists and interacts with other microorganisms in ways that may be beneficial or detrimental to the host.

Specifically, fungi have been detected in some individual tumor types and are known to contribute to carcinogenesis in malignant tumors of the esophagus and pancreas. But until now its presence, identity, location and effects in most types of cancer were unknown. Nor was any research focused on the influence of the mycobiome on immunomodulation and other states of immunosuppression associated with cancer patients known.

Fungi hiding in tumor cells

A recent investigation has changed the rules of the game. Based on the genomic analysis of 17,401 samples of tissue, blood and plasma from human tumors corresponding to 35 different types of cancer, it has highlighted that in all the tumor samples analyzed, absolutely all of them, a significant fungal load appears.

The fungi were mainly found “hiding” within tumor cells or on immune cells within tumors. Far from being isolated, they showed synergistic intratumoral interactions with the bacterioma and the set of genes and proteins that make up the immune system (immunoma).

Characteristic immune responses and multiple correlations between the presence of specific fungi in tumors and other factors related to their treatment were also found.

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Representative histological sections of four cancer types stained with hematoxylin and eosin (H&E). To the right of each one is the same microscopic field with immunofluorescence techniques, using fluorescent antibodies against α-Aspergillus and α-β-Glucan as fungal biomarkers. Modified from Narunsky-Haziza et al. 2020.

For example, breast cancer patients whose tumors contain Malassezia globosa, a common saprophytic fungus of the skin, have a much lower survival rate than those whose tumors do not contain the fungus. In addition, certain specific fungi were more prevalent in breast tumors from older patients than in younger patients, in lung tumors from smokers vs. nonsmokers, and in melanomas that responded to immunotherapy vs. non-responders.

There are also close relationships between fungi and bacteria. For example, the study suggests that tumors containing molds Aspergillus tend to be accompanied by specific bacteria, while tumors with mycelia of the genus Malassezia they tend to have different bacteria. This may have implications for treatment as the results correlate with tumor immunity and patient survival.

Fungi and bacteria to detect cancer early

It is an established fact that the presence in tumor cells of metabolically active, immunoreactive, intracellular and specific communities of bacteria and viruses of a certain type of cancer serves as its “hallmark”.

And everything points to the fact that the fungal activity of the mycobiome should become a new “hallmark” biomarker of cancer.

In light of the new results, it will be necessary to further explore the potential effects of fungi during the process of carcinogenesis and reexamine almost everything we know about this disease from the new perspective of the mycobiome.

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