In the early stages of pancreatic cancer, tumor cells establish an immunosuppressive environment that allows them to grow and divide freely, a discovery that could lead to more effective treatments for this aggressive disease.

Working with mouse models of pancreatic cancer, a team led by Dafna Bar-Sagi, PhD, of the New York University (NYU) School of Medicine in New York City, found that a mutation of the KRAS gene, which is present in 95% of all pancreatic cancers, triggers the expression of a protein known as GM-CSF. GM-CSF then directs accumulation of myeloid-derived suppressor cells in the area surrounding the tumor. These cells suppress the immune system’s natural defense against growing tumor cells.

Blocking GM-CSF production in the cancer cells disrupted the accumulation of the suppressor cells and restored the immune system’s tumor-killing response.


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“Our study suggests a therapeutic strategy for harnessing the antitumor potential of the immune system,” commented Bar-Sagi in a statement issued by NYU Langone Medical Center/NYU School of Medicine to announce the group’s results, which were published in the journal Cancer Cell (2012;21[6]:836-847).

Because the vast majority of human pancreatic cancer samples tested by the investigators expressed the GM-CSF protein prominently, Bar-Sagi expects that the findings will be applicable to a significant proportion of human pancreatic cancer cases and is hopeful that the new information will eventually lead to new drug therapies that block the production or function of the GM-CSF protein. The research may also have implications for colon, lung, and other cancers in which KRAS mutations are prevalent.