Researchers from RWJBarnabas Health and Rutgers Cancer Institute of New Jersey, the state’s top cancer facility and the only Comprehensive Cancer Center designated by the National Cancer Institute, examined the microbiome of pancreatic tumors and discovered specific microorganisms at single cell resolution that are connected to inflammation and poor survival. The fourth-leading cause of cancer death for both men and women in the United States, pancreatic cancer, may have new targets thanks to these microorganisms, say the researchers. The results are made public in Cancer Cell’s online edition.
Living things known as microbes are too small to be seen with the naked eye. Our bodies contain more microbes than there are human cells, and they can be found in organs like the pancreas, which was once thought to be microbe-free. Subhajyoti De, PhD, principal investigator at the Rutgers Cancer Institute, and Bassel Ghaddar, a graduate student in the MD/PhD program at the Rutgers Robert Wood Johnson Medical School, started looking into whether there are microbes living in pancreatic tumors and whether they have an impact on the development or treatment of cancer. But it is hard to study microbes in tumors because each patient is different and the traces left by microbes are too small to be sure of.
Martin Blaser, MD, the Henry Rutgers Chair of the Human Microbiome at Rutgers University, and the researchers joined forces to conduct additional research. To find microbes connected to specific human cells, the researchers created a genomic strategy called SAHMI (Single-cell Analysis of Host-Microbiome Interactions). Using sophisticated software, they were able to sort through millions of RNA sequences and determine which ones most likely represented human genes and which ones were microbial in origin. The results were astounding, says Dr. De, who is also an associate professor of cancer systems biology at Rutgers Robert Wood Johnson Medical School. “This new technique let us find microbes that are linked to tumors and measure the activity of the host cells at the same time,” she says. “This is a big step forward in technology.”
The team examined two distinct groups of pancreatic tumors and discovered that some of them contained bacteria that were almost entirely absent in healthy pancreatic tissues and were associated with particular cell types within the tumor. These bacteria were primarily found inside tumor cells, and their frequency correlated with the activities of cells that were involved in cancer. The specific signatures of the microbes that were discovered indicated a poor prognosis and particularly aggressive cancer progression.
The presence of microbial traces inside the pancreatic tumors made it unclear whether the immune cells there were fighting the cancer or the microbes. According to the study’s findings, the immune system was primarily attacking the microbes in the tumor rather than the cancer cells. Dr. Blaser, who is also a research associate at the Rutgers Cancer Institute and a professor of epidemiology and biostatistics at the Rutgers School of Public Health, states that “our observations provide a new view about why pancreatic cancers are so difficult to treat.” But a deeper understanding of these interactions might reveal fresh therapeutic trajectories.
