The tumour microbiome influences immune response and survival in pancreatic cancer.
It is known that the composition and diversity of the gut microbiome can affect how cancer immunotherapy works, however, little research has focused on the bacteria in the tumour, or the tumour microbiota, and how it affects prognosis and survival. Now, a study from researchers at MD Anderson Cancer Center shows that the tumour microbiome influences immune response and patient survival in pancreatic cancer, using a fecal microbiota transplant as the possible treatment. The team state their study demonstrates that pancreatic tumour 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 that 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 tumours 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’ tumours had 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 tumour microbiome a predictor of survival for surgical patients. Data findings show that long-term survival patient had an intra-tumoural microbiome signature containing Pseudoxanthomonas-Streptomyces-Saccharopolyspora-Bacillus clausii bacteria specifically, with the gut microbiome representing roughly 25% of the tumour 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’ tumours. To test the link between the tumour microbiome, the gut microbiome and immune response, the group transplanted fecal microbiota from patients with advanced cancer into mice and found that 70% of the overall tumour microbiome had been altered by the transplant; the fecal microbiota transplant was also able to affect tumour growth and tumour immune infiltration.
The team surmise their data shows the specific tumour microbiome is tied to long-term survival, and points to fecal transplant as a treatment. For the future, the reasearchers state their data suggests fecal microbiota transplants represent a significant therapeutic opportunity to improve pancreatic cancer treatment by altering the tumour immune microenvironment.