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Pancreatic cancer microbiome reveals new therapeutic targets

Written by Lauren Robertson, Science Writer.

In a study published in Cancer Cell, researchers have trawled the microbiome of pancreatic tumours and found specific microorganisms associated with inflammation and poor survival in pancreatic cancer. They hope their findings will offer new targets for earlier diagnosis and treatment of the disease.

A special relationship: Studying host-microbiome interactions

Microbiome research has really kicked it up a notch in recent years. Previously believed to be microbe-free, organs like the pancreas are now known to harbour a wide diversity of both beneficial and potentially harmful microorganisms. These microbes can contribute to increased inflammation within specific tissues and, eventually, the development of cancer. However, the mechanisms driving cancer formation – and subsequent anti-tumour responses – remain unclear.

To investigate whether any microbes were residing in pancreatic tumours (and whether they may contribute to cancer progression or outcomes), researchers from the Rutgers Cancer Institute in New Jersey began the tricky task of analysing patient microbiomes.

Due to the nature of microbiome research, they decided to team up with microbiome expert Martin Blaser (Henry Rutgers Chair of the Human Microbiome at Rutgers University) to develop a specific genomic approach for their work. Single-cell analysis of host-microbiome interactions (SAHMI) was born. This computational approach allows the identification of microorganisms associated with individual human cells by denoising microbial signals from the single-cell sequencing of host tissues.

The team then used SAHMI to sift through RNA sequencing data collected from two human pancreatic cancer cohorts and differentiate human genes from microbial ones. Importantly, their new approach allowed the researchers to look at tumour-associated microbes at the same time as measuring cell activity.

Figure 1: Graphical abstract showing the key takeaways from the paper. The denoising capability of the new SAHMI approach is outlined, along with the poor prognosis associated with the presence of certain bacteria.

Bad bacteria

They found that bacteria were associated with some specific tumour cell types (somatic cells), and that these bacteria were absent in normal pancreatic tissue. An increased abundance of these bacteria in the tissues corresponded with increased cell-type-specific gene expression and pathway activities. By incorporating multiple independent datasets, the team were able to provide a signature of cell-associated bacteria that seems to predict aggressive cancer progression and poor prognosis.

Of note, the team also discovered that most of the immune cells present in the pancreatic tumours were in fact responding to microbes rather than to cancer cells. It appears that tumour-microbiome crosstalk may impact tumorigenesis and could, therefore, have significant implications on clinical management of pancreatic cancer. “Our observations provide a new view about why pancreatic cancers are so difficult to treat,” notes Blaser. “But better understanding these interactions may identify new approaches for therapies.”