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1435 Interleukin-8 activates fibroblast and could act as a potential combinational immune-stroma therapy target
  1. Neel Nissen,
  2. Morten A Karsdal and
  3. Nicholas Willumsen
  1. Nordic Bioscience, Herlev, Denmark
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Interleukin-8 (IL-8) is a cytokine which promote tumor progression, epithelial-to-mesenchymal transition and suppress immune activation. Therefore, blockage of IL-8 has been proposed as an immunotherapy target. However, immunotherapies, of any kind, might be insufficient if the stromal fibrotic barrier surrounding the tumors is not bypassed, as immune cells have been shown to be inactivated in the tumor fibrotic space. Many cytokines have shown to module the extracellular matrix (ECM). Thus, in this study we investigated if IL-8 have ECM-modulatory properties, and could potentially act as a combinational immune-stroma therapy target.

Methods Humane pancreatic fibroblasts were cultured in Ficoll-media. Fibroblasts were treated w/wo TGF-β (1ng/mL) or IL-8 (1 and 10 ng/mL). The fibrotic activity of the fibroblasts was investigated by measuring the formation of type III collagen in the supernatant (PRO-C3) at days 3, 6, 9 and 12. Cell-viability was evaluated by Alamar-blue.

Results The formation of type III collagen (PRO-C3) was significantly increased when fibroblasts were treated with TGF-β at days 6, 9 and 12 compared to no treatment. At day 9 and 12 PRO-C3 was also significantly increased in supernatant from fibroblasts treated with IL-8 compared to no treatment.

Conclusions In this study we show that IL-8 stimulate type III collagen production in fibroblasts similar to the pro-fibrotic cytokine TGF-β. Therefore, inhibiting IL-8 could potentially be two-sided and act as both an immune-modulatory and an anti-tumor fibrotic drug.

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