IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma

Sci Rep. 2018 Apr 11;8(1):5808. doi: 10.1038/s41598-018-24194-5.

Abstract

The precise role of tumor associated macrophages remains unclear in pancreatic ductal adenocarcinoma (PDAC) while TGF-ß has an unclear role in metastases formation. In order to understand the role of IL23, an interleukin associated with macrophage polarization, we investigated IL23 in the context of TGF-ß expression in PDAC. We hypothesized that IL23 expression is associated with metastatic development and survival in PDAC. We investigated IL23 and TGF-ß protein expression on resected PDAC patient tumor sections who were divided into short-term (<12 months) survivors and long-term (>30 months) survivors. Panc-1 cells treated with IL23, TGF-ß, macrophages, or combinations thereof, were orthotopically implanted into NSG mice. Patients in the long-term survivor group had higher IL23 protein expression (P = 0.01). IL23 expression was linearly correlated with TGF-ß expression in patients in the short-term survivor group (P = 0.038). Macrophages induce a higher rate of PDAC metastasis in the mouse model (P = 0.02), which is abrogated by IL23 and TGF-ß treatment (P < 0.001). Macrophages serve a critical role in PDAC tumor growth and metastasis. TGF-ß contributes to a less tumorigenic TME through regulation of macrophages. Macrophages increases PDAC primary tumor growth and metastases formation while combined IL23 and TGF-ß pre-treatment diminishes these processes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Carcinoma, Pancreatic Ductal / pathology*
  • Disease Models, Animal
  • Humans
  • Immunohistochemistry
  • Interleukin-23 Subunit p19 / analysis*
  • Macrophages / drug effects*
  • Macrophages / immunology*
  • Mice
  • Middle Aged
  • Neoplasm Metastasis / prevention & control*
  • Survival Analysis
  • Transforming Growth Factor beta / analysis*

Substances

  • IL23A protein, human
  • Interleukin-23 Subunit p19
  • Transforming Growth Factor beta