IFN-γ synergism with poly I:C reduces growth of murine and human cancer cells with simultaneous changes in cell cycle and immune checkpoint proteins

Zachary P. Guinn, Thomas M. Petro

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Previously, we reported that IFN-γ and poly I:C, a TLR3 Pattern Recognition Receptor (PRR) agonist, reduces growth of and induces Cleaved-Caspase-3, ISG54 and p27Kip in B16 melanoma cells. Here, analysis of IFN-γ/PRR synergism was expanded with UM-SCC1 and UM-SCC38 human squamous carcinoma cells and other PRR agonists. As in B16 cells, poly I:C plus IFN-γ synergism reduced UM-SCC1 and UM-SCC38 growth, and no more than 24 h was needed for significant growth reduction. IFN-γ synergism to stem B16 growth also occurred with TLR7, TLR9, TLR4, and STING agonists, but not TLR2 agonist. IFN-γ synergized with TLR3 and TLR4 agonists reducing UM-SCC1 growth, and with TLR7 and TLR3 agonists reducing UM-SCC38 growth. IFN-γ plus poly I:C, which had the most pronounced effect, decreased cyclin-D1, increased G1 cell cycle arrest, and increased Cleaved caspase-3 in B16 cells, as well as RAW264.7, a virus-transformed murine macrophage cell line. Finally, IFN-γ plus poly I:C modulated total but not cell surface expression of immune checkpoint protein PD-L1, as well as cell cycle checkpoint proteins in B16 cells. Thus IFN-γ plus poly I:C, and other PRR agonists, may well be effective adjuvants to cancer immunotherapy against several tumor cell types.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalCancer Letters
Volume438
DOIs
StatePublished - Dec 1 2018

Keywords

  • B16 melanoma
  • IFN-γ
  • PRR agonists
  • Poly I:C
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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