Fungi Are Living in Human Tumors
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A large collaborative study by the Weizmann Institute of Science and the University of California San Diego (UCSD) has discovered multiple species of fungi living within human tumors. The research is published in Cell.
The tumor microbiome
Over a century ago, scientists discovered bacteria living in human tumors. In subsequent years, researchers have endeavored to characterize what is now known as the “tumor microbiome”, the rich collection of microorganisms that can be found within different types of tumors and their microenvironments. Advances in analytical technologies and genomic sequencing have progressed this work, such that cancer-type specific bacteria and viruses are now regarded as cancer “hallmarks”.
“The modulation by distinctive microbiomes in individual patients of the intertwined parameters of (i) eliciting (innate) tumor promoting inflammation and (ii) escaping (adaptive) immune destruction can be associated not only with prognosis, but also with responsiveness or resistance to immunotherapies involving immune checkpoint inhibitors and other therapeutic modalities,” writes Professor Douglas Hanahan, director emeritus of the Swiss Institute for Experimental Cancer Research at EPFL in Lausanne, Switzerland.
The first pan-cancer mycobiome
Fungi can be complex multicellular organisms, making their study more challenging than viruses and bacteria. Consequently, their potential role within the tumor microbiome has been unclear.
Fungi facts
It is estimated that there are over 6 million species of fungi in the world – a species richness that rivals that of plants. Fungal habitats range from water, soil and organisms. Many species fungi have yet to be discovered; however, the three major groups are:
- Multicellular filamentous molds
- Macroscopic filamentous fungi
- Single-celled microscopic yeasts
In the journal Cell, a collaborative team of scientists has published the first pan-cancer mycobiome: an atlas of the fungal communities found in over 17,000 tissue and blood samples obtained from patients presenting with 35 different types of cancer.
They found that fungi could be detected across all types of cancer, and existed mostly within immune cells inside tumors, or the cancerous cells.
Fungal activity as a hallmark of cancer
There were notable differences in the fungal compositions of cells from different types of cancers, and correlations between fungi detection and responses to pharmacological treatment. For instance, patients presenting with breast cancer where Malassezia globosa was detected had much lower survival rates when compared to patients that did not have that specific fungus.
Certain fungi were identified at higher levels in breast tumors from older patients vs younger patients, in lung tumors obtained from smokers vs non-smokers and in melanoma tumors that did not respond to immunotherapy.
The study data emphasize the utility of fungal activity as an “emerging hallmark of cancer”, says Professor Ravid Straussman of the Weizmann’s Molecular Cell Biology Department, coleader of the study. “These findings should drive us to better explore the potential effects of tumor fungi and to re-examine almost everything we know about cancer through a ‘microbiome lens.’”
In addition to analyzing fungal DNA present in patient samples, the researchers also looked at bacteria and immune cells, identifying “hubs” between fungi and bacteria communities. Tumors containing Aspergillus were often found to have specific bacteria within them, while tumors that contain Malassezia fungi were typically associated with a different species of bacteria. The researchers suggest that the “hubs” could be used to stratify patients, as they were found to be associated with tumor immunity and prognosis.
“The existence of fungi in most human cancers is both a surprise and to be expected,” says Professor Rob Knight from the department of pediatrics at UCSD School of Medicine, a co-lead author of the study. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth and skin, where bacteria and fungi interact as part of a complex community,” he concludes.
Whether or not fungi could have a causal effect in the development of cancer remains to be understood, a Tweet from Straussman implies:
Reference: Narunsky-Haziza L, Sepich-Poore GD, Livyatan I, et al. Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions. Cell. 2022;185(20):3789-3806.e17. doi: 10.1016/j.cell.2022.09.005.
