Immunomodulatory antitumor effect of interferon‑beta combined with gemcitabine in pancreatic cancer

Amber Blaauboer, Peter M. Van Koetsveld, Dana A.M. Mustafa, Jasper Dumas, Fadime Dogan, Suzanne Van Zwienen, Casper H.J. Van Eijck, Leo J. Hofland*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)


Resistance to gemcitabine is common and criti- cally limits its therapeutic efficacy in patients with pancreatic cancer. Interferon-beta (IFN-β) induces numerous antitumor effects and synergizes with gemcitabine treatment. The immunomodulatory effects of this treatment regimen have not yet been described. In the present study, the antitumor effect of IFN-β combined with gemcitabine was investigated in immune competent mice. Mouse KPC3 cells were used in all experiments. Treatment effects were determined with cell proliferation assay. Reverse transcription-quantitative PCR was used to measure gene expression. For in vivo experiments, cells were subcutaneously injected in immune competent mice. For immune profiling, NanoString analysis was performed on tumor samples of treated and untreated mice. Baseline expression of Ifnar-1 and Ifnar-2c in KPC3 cells was 1.42±0.16 and 1.50±0.17, respectively. IC 50 value of IFN-β on cell growth was high (>1,000 IU/ml). IFN-β pre-treatment increased the in vitro response to gemcitabine (1.3-fold decrease in EC 50; P<0.001). In vivo, tumor size was not statistically significant smaller in mice treated with IFN-β plus gemcitabine (707±92 mm 3 vs. 1,239±338 mm 3 in vehicle-treated mice; P=0.16). IFN-β alone upregulated expression of numerous immune-related genes. This effect was less pronounced when combined with gemcitabine. For the first time, to the best of our knowledge, the immunomodu- latory effects of IFN-β, alone and combined with gemcitabine, in pancreatic cancer were reported. Prognostic markers for predicting effective responses to IFN-β therapy are urgently needed.

Original languageEnglish
Article number97
JournalInternational Journal of Oncology
Issue number2
Publication statusPublished - Aug 2022

Bibliographical note

Funding Information:
The authors would like to thank the animal welfare takers Kim van der Leest and Lisette Dinnessen (Erasmus Medical Center, Rotterdam, The Netherlands) for their help during the mouse experiments.

Publisher Copyright:
© 2022 Spandidos Publications. All rights reserved.


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