A crucial part of our defence against disease, the composition and diversity of the gut microbiome can even affect how cancer immunotherapy works. However, little research has focused on the the tumor microbiota, and how it affects prognosis and survival. Now, a study from researchers at MD Anderson Cancer Center shows the tumor microbiome influences immune response and patient survival in pancreatic cancer, using a fecal microbiota transplant as the possible treatment. The team states their study demonstrates how pancreatic tumor microbiome composition, which cross-talks to the gut microbiome, influences the host immune response and survival rates. The study is published in the journal Cell.
Previous studies show the majority of patients with pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer, have late-stage disease when diagnosed, with just 9% surviving to five years. Patients with earlier stage cancer which can be surgically removed have a median survival of only 24-30 months. To date, no genomic biomarkers have been identified to shed light on the reasons for long-term survival rates in patients. The current study investigates whether specific microbiota has a role in pancreatic cancer survival rates.
The current study analyzes the microbiome in pancreatic tumors of 22 long-term survivors, with a median survival of 10 years, matched to 21 short-term survivors, with a median survival of 1.6 years. Results show the long-term survivors’ tumors had a much greater diversity of bacterial species than the short-term survivors, and this diversity is independent of previous therapies, body mass index or antibiotics use, making the tumor microbiome a predictor of survival for surgical patients. Data findings show long-term survival patients had an intra-tumoural microbiome signature containing Pseudoxanthomonas-Streptomyces-Saccharopolyspora-Bacillus clausii bacteria specifically, with the gut microbiome representing roughly 25% of the tumor microbiome.
The lab observed a strong correlation between immune infiltration, activation of T cells, and the three enriched bacterial types identified on long-term survivors’ tumors. To test the link between the tumor microbiome, the gut microbiome, and immune response, the group transplanted fecal microbiota from patients with advanced cancer into mice and found 70% of the overall tumor microbiome had been altered by the transplant; the fecal microbiota transplant was also able to affect tumor growth and tumor immune infiltration.
The team surmises their data shows the specific tumor microbiome is tied to long-term survival and points to fecal transplant as a treatment. For the future, the researchers state their data suggests fecal microbiota transplants represent a significant therapeutic opportunity to improve pancreatic cancer treatment by altering the tumor immune microenvironment.
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