Locally targeting the IL-17/IL-17RA axis reduced tumor growth in a Murine B16F10 melanoma model

Ya Shan Chen, Tse Hung Huang, Chao Lin Liu, Hui Shan Chen, Meng Hua Lee, Hsin Wei Chen, Chia Rui Shen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

18 Scopus citations

Abstract

Interleukin (IL)-17 and the cells that produce it within the tumor microenvironment appear to promote tumor development and are associated with survival in cancer patients. Here we investigated the role of the IL-17/IL-17 receptor A (IL-17RA) axis in regulating melanoma progression and evaluated the therapeutic potential of blocking the IL-17/IL-17RA pathway. First, recombinant mouse IL-17 (γmIL-17) treatment significantly increased proliferation of mouse B16F10 cells and human A375 and A2058 cells. Silencing IL-17RA by small hairpin RNA (shRNA) in B16F10 cells reduced the γmIL-17-elicited cell proliferation, migration, and invasion, and significantly reduced vascular endothelial growth factor and matrix metalloproteinase production. Remarkably, knockdown of IL-17RA led to a significantly decreased capability of B16F10 cells to form tumors in vivo, similar to that in IL-17-deficient mice. Finally, local application of an adenovirus delivering a shRNA against IL-17RA mRNA not only significantly suppressed tumor development, but also enhanced antitumor immunity by increasing the interferon γ-expressing T cells and not T regulatory cells. Our results highlight the critical role of the IL-17/IL-17RA pathway in tumor progression and imply that targeting IL-17RA represents a promising therapeutic strategy.

Original languageEnglish
Pages (from-to)273-285
Number of pages13
JournalHuman Gene Therapy
Volume30
Issue number3
DOIs
StatePublished - 03 2019

Bibliographical note

Publisher Copyright:
© Mary Ann Liebert, Inc., publishers 2019.

Keywords

  • IL-17
  • IL-17RA
  • adenovirus
  • gene therapy
  • melanoma
  • shRNA

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