Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the world. Mostly chemoresistant, PDAC so far has no effective treatment. Understanding the connective tissue, called stroma, that surrounds, nurtures, and even protects PDAC tumors, is key to developing effective therapeutics. "PDAC patients are diagnosed really late, so we don't know they're sick until the very end stages," said Ela Elyada (photo), PhD, a postdoctoral fellow in Dr. David Tuveson's lab at Cold Spring Harbor Laboratory (CSHL) in New York. "We can't diagnose patients early enough because we don't have tools, and they don't respond to drugs. One barrier to the drugs is the fibroblasts in the stroma." PDAC is characterized by an abundance of non-malignant stromal cells, and fibroblasts are one of the most common types of stromal cells. "We have a lot of fibroblasts in pancreatic cancer, unlike other cancers which are mostly cancer cells," Dr. Elyada said. These cancer-associated fibroblasts (CAFs) can help cancer cells proliferate, survive, and evade detection by the immune system. The insidious role CAFs seem to play in protecting cancer cells labels them as bad, but completely obliterating CAFs in mice also worsened their cancers. Dr. Elyada wanted to investigate the nature of CAFs: are they good or bad? To crack the case, she, Associate Professor Paul Robson at the Jackson Laboratory, and colleagues used single-cell RNA sequencing to classify the fibroblasts into three distinct sub-populations, identifying specific functions and characteristics unique to each. This includes two previously identified types of CAFs, myofibroblastic CAFs (myCAFs) and inflammatory CAFs (iCAFs), and also a new type of CAF called antigen-presenting CAFs (apCAFs). The apCAFs were present in both mice and human PDAC.
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