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The IL-17A/IL-17RA Axis Is Not Related to Overall Survival and Cancer Stem Cell Modulation in Pancreatic Cancer

1
Department of General, Visceral, Tumor and Transplantation Surgery, University Hospital of Cologne, Kerpener Straße 62, 50937 Cologne, Germany
2
Institute of Pathology, University Hospital of Cologne, Kerpener Straße 62, 50937 Cologne, Germany
3
Department of General, Visceral und Vascular Surgery, Otto von Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany
4
Institute for Pathology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(6), 2215; https://doi.org/10.3390/ijms21062215
Received: 14 February 2020 / Revised: 18 March 2020 / Accepted: 21 March 2020 / Published: 23 March 2020
(This article belongs to the Special Issue Cell and Molecular Biology of Pancreatic Disorders 2019)
(1) Background: IL-17A accelerates pancreatic intraepithelial neoplasia (PanIN) progression. In this study, we examined whether IL-17A/IL-17RA promotes pancreatic ductal adenocarcinoma (PDAC) aggressiveness in terms of survival and cancer stem cell modulation. (2) Methods: In vitro, the wound-healing assay, the sphere formation assay, and flow cytometry were applied to assess cancer stem cell features. In vivo, pancreatic tumors were induced in C57BL/6 mice using electroporation with oncogenic plasmids (P53-/- R172H; KrasG12V). Anti-IL-17 antibodies were administered as immunotherapy. We analyzed IL-17A/IL-17RA related survival using publicly available transcriptomic data (n = 903). (3) Results: IL-17A/IL-17RA expression was not related to survival in PDAC patients. IL-17A neither induces stem cell markers nor increases sphere formation and cell motility in vitro. Blocking the IL-17A/IL-17RA axis in a murine pancreatic cancer model did not improve the survival of mice, but reduced the tumor burden slightly. (4) Conclusions: IL-17A does not promote stem cell expansion in PDAC cell lines. Blocking IL-17A/IL-17RA signaling does not interfere with pancreatic cancer development and progression and may not be considered as a promising monotherapy for PDAC. View Full-Text
Keywords: pancreatic cancer; immunotherapy; IL-17A; IL-17RA; cancer stem cell pancreatic cancer; immunotherapy; IL-17A; IL-17RA; cancer stem cell
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Li, J.; Betzler, C.; Lohneis, P.; Popp, M.C.; Qin, J.; Kalinski, T.; Wartmann, T.; Bruns, C.J.; Zhao, Y.; Popp, F.C. The IL-17A/IL-17RA Axis Is Not Related to Overall Survival and Cancer Stem Cell Modulation in Pancreatic Cancer. Int. J. Mol. Sci. 2020, 21, 2215.

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