Serum cytokine levels are associated with tumor progression during FOLFIRINOX chemotherapy and overall survival in pancreatic cancer patients

Fleur van der Sijde, Willem A. A. Dik, Dana A. M. Mustafa, Eveline E. E. Vietsch, Marc G. G. Besselink, Reno Debets, Bas Groot Koerkamp, Brigitte C. M. Haberkorn, Marjolein Y. V. Homs, Quisette P. P. Janssen, Saskia A. C. Luelmo, Leonie J. M. Mekenkamp, Astrid A. M. Oostvogels, Marja A. W. Smits-te Nijenhuis, Johanna W. W. Wilmink, Casper H. J. van Eijck*

*Corresponding author for this work

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BackgroundBiomarkers predicting treatment response may be used to stratify patients with pancreatic ductal adenocarcinoma (PDAC) for available therapies. The aim of this study was to evaluate the association of circulating cytokines with FOLFIRINOX response and with overall survival (OS). MethodsSerum samples were collected before start and after the first cycle of FOLFIRINOX from patients with PDAC (n=83) of all disease stages. Overall, 34 circulating cytokines were analyzed with a multiplex immunoassay. In addition, changes in peripheral blood immune cell counts were determined by flow cytometry to correlate with differences in cytokine levels. Chemotherapy response was determined by CT scans with the RECIST 1.1 criteria, as disease control (n=64) or progressive disease (n=19) within eight cycles of FOLFIRINOX. ResultsPatients with high serum IL-1RA concentrations after one cycle of chemotherapy were less likely to have tumor progression during FOLFIRINOX (OR 0.25, P=0.040). Increase of circulating IL-1RA concentrations correlated with increase of total, classical (CD14+CD16-), and non-classical monocytes (CD14-CD16+), and dendritic cells. In multivariable cox regression, including the variables chemotherapy response outcome and baseline CA19-9 level, serum concentrations of IL-7 (HR 2.14, P=0.010), IL-18 (HR 2.00, P=0.020), and MIP-1 beta (HR 0.51, P=0.025) after one cycle of FOLFIRINOX showed correlations with OS. ConclusionsCirculating IL-1RA, IL-7, IL-18, and MIP-1 beta concentrations are biomarkers associated with FOLFIRINOX response in PDAC patients, suggesting an important role for specific immune cells in chemotherapy response and PDAC progression. Cytokine-based treatment might improve patient outcome and should be evaluated in future studies.
Original languageEnglish
Article number898498
Number of pages12
JournalFrontiers in Immunology
Publication statusPublished - 25 Aug 2022

Bibliographical note

Funding Information:
This research was funded in part by the Support Casper foundation and by the Eurostars project (project number ESTAR17104).

Publisher Copyright:
Copyright © 2022 van der Sijde, Dik, Mustafa, Vietsch, Besselink, Debets, Koerkamp, Haberkorn, Homs, Janssen, Luelmo, Mekenkamp, Oostvogels, Smits-te Nijenhuis, Wilmink, van Eijck and the Dutch Pancreatic Cancer Group.


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