Tumor microbiome associated with successful immunotherapy in patients with sarcoma

(SACRAMENT) In a significant new study, researchers at the Comprehensive Cancer Center at UC Davis have discovered a link between a patient’s microbiome and their immune system that could potentially be used to improve the treatment of soft tissue sarcoma. This type of cancer is found in connective tissues like muscle, fat and nerves.

The results of the study were published in the Journal for Immunotherapy of Cancer.

“The study data show new lines of research in the paradigm-shifting concept that a patient’s microbiome and their immune system can interact with and shape each other, as well as potentially be engineered to improve patient outcomes,” said Robert Canter, the study’s lead author and head of the Division of Surgical Oncology.

The gut microbiome is made up of microorganisms in the digestive tract that include bacteria, fungi, and viruses. Microbial communities were also found in other parts of the body, including the mouth, lungs and skin. And now the study shows that they are also found in tumor cells.

“We found that soft tissue sarcomas harbor a quantifiable amount of microbiome within the tumor environment. Most importantly, we found that the amount of the microbiome at the time of diagnosis may be linked to the patient’s prognosis,” added Canter.

Although the levels of microbes are low, the study results are significant because many tumors, especially sarcomas, were considered sterile.

We found that soft tissue sarcomas harbor a quantifiable amount of microbiome within the tumor environment. Most importantly, we found that the amount of the microbiome at the time of diagnosis may be linked to the patient’s prognosis.”Robert Canter, Chief, Division of Surgical Oncology at UC Davis

Viruses within the microbiome may attract cancer-fighting cells

The UC Davis researchers also discovered how the microbiome within a sarcoma tumor plays a role in attracting specific types of immune cells, such as natural killer cells that fight cancer. Canter said this is important because the higher the rate of natural killer cell infiltration into a tumor, the greater the chance that the sarcoma will not spread to other parts of the body. Natural killer cells are a key target for improving the effectiveness of immunotherapy.

Large tumor located above the knee of a man wearing shorts.
Large soft tissue mass of the medial thigh suspected of soft tissue sarcoma in a patient who participated in the study.

The team found that viruses within a tumor’s microbiome appear to affect the amount of natural killer cells found in sarcomas and, for that reason, affect survival rates. Specifically, the study found a strong positive correlation between the presence of Respirovirus, a genus of viruses known to cause respiratory illness, and the presence of natural killer cells in the tumor. Canter and his colleagues are now considering ways to engineer viruses to attract more cancer-killing immune cells.

“It became clear that the microbiome in the gut and elsewhere in the body has a major impact on human health and disease. Surprisingly, it shapes the immune system throughout the body, and because of its interaction with the immune system, we now know that it also plays a huge role in how the body responds to cancer and cancer treatments such as immunotherapy.” said Canter.

cross campus collaboration

The authors obtained tumor and stool samples from 15 adult patients with non-metastatic soft tissue sarcoma, who were studied for an average of 24 months. Analysis revealed that the majority of tumors were advanced stage III (87%) and affected a patient’s limb (67%).

Tissue samples were sent to the university’s Genome Center in Davis for sequencing and to the Flow Cytometry Shared Resources Laboratory at the UC Davis Medical Campus in Sacramento for immunological profiling. The patients were monitored for two years as part of their cancer treatment follow-up.

Canter said previous research has shown the existence of microbiome within tumors in several types of cancer, including breast, lung, pancreas and melanoma. For that reason, he said more research into the connection between the microbiome and the immune system in other cancers is needed.

Thanks

Study co-authors are Lauren Perry, Sylvia Cruz, Kara Kleber, Sean Judge, Morgan Darrow, Louis Jones, Ugur Basmaci, Nikhil Joshi, Matthew Settles, Blythe Durbin-Johnson, Alicia Gingrich, Arta Monjazeb, Janai Carr-Ascher, Steven Thorpe , William Murphy and Jonathan Eisen.

This work was supported by the UC Davis Comprehensive Cancer Center and the UC Davis Flow Cytometry Shared Resource Laboratory, with funding from the National Cancer Institute grants P30 CA093373, S10 OD018223, and S10 RR 026825. Samples were provided by the UC Davis Pathology Biorepository, funded by the Comprehensive Cancer at UC Davis and the Department of Pathology and Laboratory Medicine at UC Davis. Sequencing was performed at DNA Technologies and Expression Analysis Cores at the UC Davis Genome Center, funded by National Institutes of Health (NIH) Shared Instrumentation Grant 1S10OD010786-01.

Comprehensive Cancer Center at UC Davis

The UC Davis Comprehensive Cancer Center is the only National Cancer Institute-designated center serving the Central Valley and interior of Northern California, a region of more than 6 million people. Its experts provide compassionate, comprehensive care to more than 100,000 adults and children each year and access to more than 200 active clinical trials at any given time. Its innovative research program involves more than 240 UC Davis scientists working collaboratively to advance the discovery of new tools to diagnose and treat cancer. Patients have access to cutting-edge care, including immunotherapy and other targeted treatments. Its Office of Outreach and Community Engagement addresses disparities in cancer outcomes across diverse populations, and the cancer center provides comprehensive education and workforce development programs for the next generation of physicians and scientists. For more information, visit cancer.ucdavis.edu.

Tumor microbiome associated with successful immunotherapy in patients with sarcoma

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