Study reveals cellular cross-talk between regulatory T cells and fibroblast cells in pancreatic cancer microenvironment

A multidisciplinary Michigan Medicine team is shedding new light on the role of regulatory T cells in pancreatic cancer -; and, in mouse models, have uncovered a new potential target to improve immunotherapy approaches to the deadly disease.

Regulatory T cells are a subpopulation of immune cells that help keep the immune system from going overboard and running amok, but if the system is tamped down too much it can end up protecting cancer cells from the body's own defenders.

Our study focused on the role of regulatory T cells during the onset and progression of pancreatic cancer, which is poorly understood. Contrary to our expectations, we found that depleting the regulatory T cells actually made tumor cells more aggressive and sped up the cancer's progression."

Filip Bednar, M.D., Ph.D., study co-senior author and assistant professor of Surgery, Michigan Medicine

Bednar is also a member of the U-M Rogel Cancer Center.

That's because there appear to be several parallel immunosuppression mechanisms at work, and removing one of them via the removal of the regulatory T cells allows for others to take its place and help tumors grow, the team reported in Cancer Discovery.

The team's findings point toward a particular chemokine receptor that might be additionally targeted to help overcome immunosuppression when treating pancreatic cancer.

New treatment approaches are desperately needed, Bednar notes. Pancreatic cancer is one of the deadliest cancers, with a five-year survival rate around 9%.

"Our work reveals complex cellular cross-talk between regulatory T cells and fibroblast cells within the pancreatic cancer microenvironment," says study lead author Yaqing Zhang, M.D., Ph.D., a member of the lab of senior author Marina Pasca Di Magliano, Ph.D. "It also provides evidence that different fibroblast cells have different, even opposing functions, in the development of pancreatic cancer."

Source:
Journal reference:

Zhang, Y. et al. (2020) Regulatory T cell depletion alters the tumor microenvironment and accelerates pancreatic carcinogenesis. Cancer Discovery. doi.org/10.1158/2159-8290.CD-19-0958.

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