Experts Find Potential Markers of OS in Pancreatic Ductal Adenocarcinoma
Study findings suggest that low cytoplasmic Wilms' tumor 1 (WT1) expression in pancreatic ductal adenocarcinoma (PDA) cells and sustained low levels of a granulocyte-related systemic inflammatory response following the early period of therapy may be used to predict overall survival (OS) in patients with PDA who are receiving WT1-targeting immunochemotherapy (Oncology. 2019;97:135-148).
“We have developed a…[WT1]-targeting dendritic cell (DC)-based cancer vaccine combined with standard chemotherapy for patients with advanced [PDA],” explained lead investigator Zensho Ito, MD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Japan, and colleagues.
The purpose of the study by Dr Ito et al was to assess predictive markers of OS in patients with PDA given multiple major histocompatibility complex class I/II-restricted, WT1 peptide-pulsed DC vaccinations (DC/WT1-I/II) plus chemotherapy.
In addition to evaluating the plasma levels of soluble factors derived from granulocytes of 7 patients with PDA, the investigators assessed cytoplasmic WT1 expression and systemic inflammatory response markers (ie, neutrophil-to-lymphocyte ratio [NLR], monocyte-to-lymphocyte ratio [MLR], and granulocyte-to-lymphocyte ratio [GLR]).
“Compared to the 4 non-super-responders (OS <1 year), the remaining 3 super-responders (OS ≥1 year) showed significantly decreased low plasma matrix metalloproteinase-9 levels throughout long-term therapy,” Dr Ito and co-investigators reported.
After 5 DC/WT1-I/II vaccinations and 3 gemcitabine therapy cycles, the NLR, MLR, and GLR were significantly lower among super-responders versus non-super-responders.
Of note, super-responders had relatively weak cytoplasmic WT1 expression in their PDA cells compared with non-super-responders.
“Prolonged low levels of a granulocyte-related systemic inflammatory response after the early period of therapy and low cytoplasmic WT1 expression in PDA cells may be markers predictive of OS in PDA patients receiving WT1-targeting immunochemotherapy,” Dr Ito and colleagues said.—Hina Porcelli