Fungi are not just the pesky organisms causing athlete's foot or thrush. They are actually an important part of our immune system, and when things go wrong, they can even contribute to disease. In fact, recent research has found that fungi may play a role in cancer development. While they have been detected in some individual tumor types, their presence and impact across a broad range of cancers remains largely unknown.
So far, researchers have detected fungi in 35 different types of cancer, with some types of fungi found to be more common in certain cancers. For example, Candida and Malassezia were more often found in esophageal cancer, while Aspergillus and Cryptococcus were more prevalent in pancreatic cancer. In addition, the fungi were often found inside cancer cells, suggesting they may be playing an active role in tumor development.
Despite the growing evidence of fungi's involvement in cancer, much remains unknown about their effects. Researchers are still trying to determine whether fungi contribute directly to cancer development or whether they simply take advantage of the weakened immune systems of cancer patients. Furthermore, the specific mechanisms by which fungi interact with cancer cells remain a mystery.
Given the complexity of interactions between fungi and bacteria, studying fungi in the context of tumors is crucial. By understanding the relationships between different microorganisms, researchers may be able to develop new therapies or even prevent cancer development altogether. While much remains to be discovered, the recent findings on fungi and cancer provide a promising avenue for further investigation.
In a groundbreaking discovery, researchers have identified the presence of fungal nucleic acids in many different types of human cancers. They conducted a study using two large cohorts of cancer samples previously examined for bacteria, and profiled fungal DNA in all samples to determine fungal presence.
To ensure the accuracy of their findings, the researchers used a combination of whole genome sequencing (WGS) and transcriptome sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA). They also performed quality control measures by re-aligning all unmapped DNA and RNA reads to a uniform human reference.
Through their analysis, the researchers found that all tumor types tested had a higher fungal load than negative controls. Additionally, they observed significant, cancer type-specific differences in the percentage of classified fungal, bacterial, and pan-microbial reads of the total or unmapped reads in 31 of the 32 cancer types studied. Interestingly, they also found that fungal and bacterial read proportions had high Spearman correlations.
The researchers calculated per-sample and aggregate fungal genome coverages across all WGS and RNA-seq samples, and identified 31 different fungi with greater than 1% aggregate genome coverage. Furthermore, they found that the WIS-TCGA overlapping fungi were significantly more likely to have greater than 1% aggregate genome coverage.
Despite the different advantages and drawbacks of the WIS and TCGA cohorts, the researchers were able to identify 87.2% of WIS species and 93.4% of fungal genera in matched TCGA cancer types. These findings highlight the importance of further research into the role of fungi in cancer development and the potential for new therapies based on these discoveries.
The visualization of fungi in human tumors has been a challenging task due to the limitations of current staining methods. However, researchers have recently developed a method that integrates four staining techniques with varying levels of sensitivity and specificity to detect fungi in human tumors. In doing so, they have been able to identify the presence of fungal elements in a number of cancer types, including melanoma, pancreas, breast, lung, and ovarian cancer.
Using this technique, the researchers found that between 0% to 25% of tumors per cancer type were positive for either b-glucan or Aspergillus staining. These findings suggest that fungal presence in tumors is not uniform, and that further research is needed to determine the factors that contribute to the presence or absence of fungi in different types of cancer.
In addition, the researchers also found that mycobiome richness varied significantly across different cancer types in both the WIS and TCGA cohorts. Interestingly, they found that tumor bacterial richness was significantly higher than fungal richness. However, four of the seven cancer types shared by both cohorts showed significant positive correlations between intratumoral fungal and bacterial richness. These findings suggest a complex interplay between different microorganisms in tumors, and highlight the importance of further research into the interactions between fungi and bacteria in cancer development.
Overall, these findings shed light on the previously understudied role of fungi in cancer development and provide a promising avenue for the development of new cancer therapies.
The tumor microenvironment is a complex and dynamic system involving a multitude of interactions between different microorganisms and immune cells. To better understand these interactions, researchers conducted a study to investigate the intratumoral mycobiome-bacteriome-immunome interactions in different types of cancer.
The researchers found that the intratumoral mycobiome alpha diversity was low, but beta diversity was high between tumor samples. Across WIS cancer types, Ascomycota and Basidiomycota phyla dominated the intratumoral mycobiome. The Ascomycota to Basidiomycota ratio (A/B ratio) was highest in colon cancer due to abundant Saccharomycetes, and lowest in melanoma.
Fungi and bacteria were found to interact with each other through physical and biochemical mechanisms. The most significant interdomain co-occurrences were found in breast cancer, which had the most samples, with 96.5% of significant fungi-bacteria co-occurrences in breast cancer being positive.
Furthermore, the researchers hypothesized that intratumoral fungal-bacterial-immune clusters exist and compared WIS-overlapping fungal and bacterial genera in TCGA with TCGA immune cell compositions. Through unsupervised analyses, they were able to identify three distinct fungi-bacteria-immune clusters driven by fungal co-occurrences. Raw counts were then aggregated within each domain and mycotype to form log-ratio comparisons.
The researchers found that the log-ratios of immune cells co-occurring with F1, F2, or F3-clustered fungi significantly separated immune response subtypes, suggesting that different cancer types exhibit distinct mycobiomes that drive different immune responses.
Overall, these findings demonstrate the complex and interdependent interactions between different microorganisms and immune cells in the tumor microenvironment. By better understanding these interactions, researchers may be able to develop new therapies that target specific microorganisms or immune responses to improve cancer treatment outcomes.
In addition to providing new insights into the role of fungi in cancer development, recent research has also explored the clinical utility of cancer mycobiomes as a diagnostic and prognostic tool.
Using the WIS cohort, researchers first tested fungal associations with disease phenotypes and found Cladosporium sphaerospermum and the Cladosporium genus enriched in breast tumors of patients over 50 years old. Similarly, in lung cancer, they found higher intratumoral fungal richness.
In a separate analysis, blood-derived, stage-invariant, cancer-type-specific fungal compositions in TCGA suggested their utility as minimally invasive diagnostics. These findings were validated in two independent, published cohorts.
These findings demonstrate the promising potential of the cancer mycobiome as a diagnostic and prognostic tool, especially in the context of minimally invasive diagnostics. If further validated, these findings could revolutionize cancer diagnosis and ultimately lead to better treatment outcomes for patients.
The recent groundbreaking research into the role of fungi in cancer development has shed new light on the complex interplay between microorganisms and the immune system in tumors.
By characterizing the mycobiomes of 17,401 tissue and blood samples in four independent cohorts across 35 cancer types, researchers were able to identify fungal-driven, pan-cancer "mycotypes" with distinct immune responses that stratified patient survival. These findings suggest that fungal presence in tumors may have important implications for patient outcomes, including overall survival in breast cancer, progression-free survival in ovarian cancer, and immunotherapy response in melanoma tumors.
In addition, the researchers observed strong positive correlations between fungal and bacterial diversities, abundances, and co-occurrences across several cancer types. This suggests that tumor microenvironments may be non-competitive spaces for multi-domain microbial colonization, highlighting the importance of further research into the interactions between different microorganisms in tumors.
Finally, the researchers provided the first analysis of plasma mycobiomes in treatment-naive, early-stage cancers. They found that tumor-derived WIS species provided similar performance to a multi-domain database 26-fold larger, suggesting that the cancer mycobiome may be a useful tool for early cancer detection and diagnosis.
Overall, these findings highlight the complex and previously overlooked role of fungi in cancer development and provide promising avenues for future research into new cancer therapies and diagnostics.
As we continue to learn more about the role of fungi in cancer development, it's important to consider the potential implications of these findings for our indoor living and working environments. If fungi are indeed found to be correlated with cancer, then environments that show high levels of fungi may be much more serious than just causing allergies.
When we sneeze because of a moldy environment, for example, we may be inhaling mold spores that could potentially lead to cancer. This underscores the importance of maintaining clean and healthy indoor environments, especially in areas where people spend significant amounts of time, such as homes, schools, and offices.
Ultimately, the research into the cancer mycobiome is still in its early stages, and more work is needed to fully understand the complex interactions between microorganisms and the immune system in tumors. However, the potential implications of these findings for public health and cancer prevention are significant and highlight the importance of continued research in this field.
Narunsky-Haziza L, Sepich-Poore GD, Livyatan I, Asraf O, Martino C, Nejman D, Gavert N, Stajich JE, Amit G, González A, Wandro S, Perry G, Ariel R, Meltser A, Shaffer JP, Zhu Q, Balint-Lahat N, Barshack I, Dadiani M, Gal-Yam EN, Patel SP, Bashan A, Swafford AD, Pilpel Y, Knight R, Straussman R. Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions. Cell. 2022 Sep 29;185(20):3789-3806.e17. doi: 10.1016/j.cell.2022.09.005. PMID: 36179670; PMCID: PMC9567272.DOI: ,
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