Innate association with tumors may predict worse outcomes

The presence of some innate species in tumors predicts — and may help drive — worse cancer outcomes, according to a study by Weill Cornell Medicine and Duke University researchers.

The study29 in Cell, provides a scientific framework for developing tests that identify specific fungal species in tumors relevant to predicting cancer progression and treatment. The findings also suggest that antifungal therapies can be used to augment traditional cancer treatments in some cases.

“These findings open up many exciting research directions, from the development of diagnosis and treatment to studies of the detailed biological mechanisms of innate relationships with cancer,” said the senior author. Ilyan IlievAssociate Professor of Immunology in Medicine at Department of Gastroenterology and Hepatology and member of Jill Roberts Institute for Research in Inflammatory Bowel Disease In Weill Cornell Medicine.

The study’s first author was Anders Dollmann, a PhD student in biomedical engineering at Duke University.

The idea that viruses and bacteria can stimulate or accelerate the development of cancer is now well established. However, little is known about the cancer-related roles of fungi — which, like bacteria and viruses, colonize the intestines, lungs, skin, and other barrier tissues, interact with the immune system, and sometimes cause disease.

In the new study, the researchers categorized the inbred species and their associations with different cancer diseases by analyzing the Cancer Genome Atlas, the largest well-annotated genomic database of human tumors.

The analysis showed that the DNA of some fungal species is relatively abundant in some types of tumors. These types, in gastrointestinal tumors, include Tropical Candida and Candida albicans, which cause oral thrush and fungal infections. in lung tumors, types of fungi Blastomyces; And in breast tumors, types of Malassezia fungi.

The researchers devised sophisticated computational methods to exclude fungal DNA that likely originated from laboratory contamination, and in particular were able to confirm the presence of live Candida species in colorectal tumor samples.

Their analysis linked elevated levels of Candida in gastrointestinal tumors to tumor gene activity that promotes inflammation and reduces cell-to-cell adhesion — features associated with the spread of late-stage cancer to distant organs, known as metastasis. Higher candida levels of such tumors were also directly correlated with a greater rate of metastasis.

The findings, according to the researchers, suggest that high levels of specific fungi in tumor biopsies may one day be used as biomarkers, indicating, for example, a higher risk of metastasis — which in turn could lead to more effective treatment selection.

Curiously, researchers often discovered DNA from the same Candida species in both gastrointestinal tumor samples and matched blood samples from the same patients.

“These data are exciting because they lay the foundation for simple, inexpensive candida DNA tests that can more accurately identify the prognosis of gastrointestinal cancers, and augment standard tumor DNA biopsies to enable early detection of these cancers before other signs appear.” -author Stephen LipkinD., Gladys and Roland Harriman Professor of Medicine and Vice Chair of Research in the Sanford and Joan Weill Department of Medicine in Weill Cornell Medicine. Lipkin is also the leader of the Cancer Genetics and Epigenetics Program at Sandra and Edward Mayer Cancer Center and clinical geneticist at NewYork-Presbyterian/Weill Cornell Medical Center.

It is conceivable that tumor-associated fungi could also be targets of antifungal therapies to improve overall treatment outcomes. However, this possibility hangs on an unanswered question: Do tumor-resident fungi help in causing malignancy, possibly by fueling inflammation, as some bacteria are known to do? Or is the fungi associated only with some tumors because the tumors, as they progress further, provide an increasingly permissive environment for the growth of fungi?

Iliev said the researchers plan to follow up on this and other lines of investigation in further studies.

“It is plausible that some of these fungi promote tumor development and metastases, but even if they are not, they may be of great value as prognostic indicators,” he said.

Research in Iliev’s lab is supported by the National Institutes of Health, the Institute of Cancer Research, and the Leona M. and Harry B. Fund PATH Award.

Jim Schnabel is a freelance writer at Weill Cornell Medicine.

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