Inflammation May Provide Insight into Treatment Resistance in Pancreatic Cancer

The presence of systemic inflammation in patients with advanced pancreatic cancer may point to possible resistance to CD40 agonists, according to findings from a new study.

Researchers from the Abramson Cancer Center at the University of Pennsylvania analyzed blood samples from 22 patients with advanced pancreatic ductal adenocarcinoma (PDAC) who were treated with an anti-CD40 monoclonal antibody in combination with gemcitabine. Over eight days, they observed depletion of B cells, monocytes, and dendritic cells, and T cell activation, but found no evidence of an association between these factors and clinical outcomes.

Upon analysis of inflammatory networks, the researchers did find that patients with systemic inflammation in their bloodstream had worse overall survival compared with those without inflammation, or 5.8 months versus 12.3 months, respectively (P=0.0105).

“We believe we have not only identified a potentially robust biomarker, but also important players in the immune system we didn’t see before that may drive mechanisms of resistance,” said lead author Max M. Wattenberg, MD, in a press release.

“These latest findings support the fact that inflammation seems to place the immune system at a disadvantage and in doing so prevents the ability of immune therapies to work,” said senior author Gregory L. Beatty, MD, PhD. “Next, we’re interested to learn how to pair a T cell immune response with a CD40 agonist, so we are studying combinations that will help make the inflammatory response less suppressive and the components of the immune system more capable of triggering a T-cell response.”

Results from this study were published in JCI Insight.

My ‘folklore’ of the pandemic was this manuscript just out in JCI Insight.

We studied immune determinants of response to CD40-agonist therapy, a promising treatment strategy for patients with pancreatic cancer. https://t.co/GI4zN6ayEi

— Max Wattenberg (@mmwatt02) January 28, 2021

Check out our new paper from @mmwatt02 in JCI Insight!!

“Systemic inflammation is a determinant of outcomes to CD40 agonist-based therapy in pancreatic cancer patients”https://t.co/8l7VaX5yF2

Congrats Dr. Wattenberg!! pic.twitter.com/TEAElf1yLU

— Beatty Lab (@LabBeatty) January 28, 2021