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Dismantling pancreas cancer's armor
Date:2/20/2014

ating factor (GM-CSF), which attracted the Gr-MDSCs.

Strikingly, the Gr-MDSCs actively worked against T cells, a class of immune cell central to many immunotherapy strategies. T cells are often harnessed to fight tumors because they can recognize very specific molecules and destroy any cells expressing those molecules. But Gr-MDSCs prevented T cells from dividing and even induced their death.

Stromnes found this effect could be reversed, however, and the T-cell response activated, by depleting Gr-MDSCs. When she did so, she saw evidence not only that the T cells could now enter the tumors, but also that the tumors showed evidence of the type of cellular damage the T cells are designed to mete out.

"The findings are important because they show that the tumor microenvironment itself, and in particular a specific subset of cells in the tumor, is preventing T cells from trafficking to the tumor and mounting a response," Stromnes said. Importantly, humans also possess cells very similar to Gr-MDSCs, which strengthens the case that similar strategies could impact human pancreas cancer. Additionally, the damage wreaked on Gr-MDSC-depleted tumors appeared to release some of the pressure inside the tumor, allowing crushed blood vessels to open again and providing a potential avenue for chemotherapy.

'We want to put as big a hurt on pancreas cancer as possible'

The results are a backbone on which the team can begin designing a multipronged approach to pancreas cancer therapies, Stromnes noted. The findings show that a T-cell-based therapy alone may not be enough. Researchers must also take into account pancreas cancer's immunosuppressive strategies. "We're trying to get the helpful immune cells into the tumors, and our results show that to do that, we need to get rid of these inhibitory cells the tumors have co-opted," she said.

The team is now working to develop a T-cell therapy to take advantage of their new findings.
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Contact: Kristen Woodward
media@fredhutch.org
206-667-2210
Fred Hutchinson Cancer Research Center
Source:Eurekalert  

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