Patients with pancreatic cancer who lived longer were found to have higher microbial diversity and more immune activation in their tumors, and when fecal samples from these long-term survivors were transplanted into mice, tumor growth slowed in the mice, suggesting that the tumor microbiome may influence survival outcomes among individuals with pancreatic cancer. The findings were recently published in Cell.
During an interview with Cancer Therapy Advisor, George Miller, MD, surgeon at NYU Langone’s Perlmutter Cancer Center in New York City, said that it’s been known for many cancers that a better immune infiltrate is associated with a better outcome because the immune system is the primary defense against cancer. But as far as a correlation between the tumor microbiome and survival, he said, “That’s never really been done before, and [the researchers of the Cell paper] do it in a very convincing manner.”
The study researchers started with a discovery cohort of patients from The University of Texas MD Anderson Cancer Center who had lived more than 5 years (median, 10.1 years) after surgical resection of their tumor — termed long-term survivors — and compared them with matched patients who had lived fewer than 5 years after surgery (median, 1.6 years) — termed short-term survivors. Patients from Johns Hopkins Hospital, Baltimore, Maryland, served as the validation cohort.
Between the discovery and validation cohorts, 36 long-term and 32 short-term survivor tumor samples were obtained, and bacterial DNA from the samples were profiled, revealing that the tumor samples from long-term survivors in both cohorts had a significantly more diverse bacterial species compared with short-term survivors. Also, patients with high microbial diversity survived a median of 8 years longer than those with low microbial diversity (9.66 years vs 1.66 years).
Going a step further, the study researchers identified a distinct microbial signature between the long-term and short-term survivors. Specifically, 3 taxa (Pseudoxanthomonas, Saccharropolyspora, and Streptomyces) and 1 species (Bacillus clausii) were more common in samples from long-term survivors compared with short-term survivors. Taken together, the signatures were able to help researchers predict which patients would live longer.
Turning to the immune response, the researchers found in both cohorts that long-term survivors had higher concentrations of CD8-positive (CD8+) T cells, and the higher concentrations appeared to correlate with the presence of the 3 taxa found in the long-term-survivors. These findings not only may suggest that survival is linked to immune activation, but also that immune activation may be linked to the tumor microbiome.