Activated STING-containing R-EVs from iPSC-derived MSCs promote antitumor immunity

Cancer Lett. 2024 Aug 10:597:217081. doi: 10.1016/j.canlet.2024.217081. Epub 2024 Jun 22.

Abstract

We recently revealed that activated STING is secreted into RAB22A-induced extracellular vesicles (R-EVs) and promotes antitumor immunity in cancer cells. Whether mesenchymal stem cell (MSC)-derived R-EVs containing activated STING can be used as a novel antitumor immunotherapy remains unclear, as MSC-derived EVs are promising cell-free therapeutics due to their superior biocompatibility and safety, as well as low immunogenicity. Here, we report that induced pluripotent stem cell (iPSC)-derived MSCs can generate R-EVs with a size and mechanism of formation that are similar to those of R-EVs produced from cancer cells. Furthermore, these MSC-derived R-EVs containing activated STING induced IFNβ expression in recipient THP-1 monocytes and antitumor immunity in mice. Our findings reveal that the use of MSC-derived R-EVs containing activated STING is a promising cell-free strategy for antitumor immunity.

Keywords: Antitumor immunity; Extracellular vesicles; Mesenchymal stem cells; RAB22A; Rafeesome; STING.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Extracellular Vesicles* / immunology
  • Extracellular Vesicles* / metabolism
  • Humans
  • Induced Pluripotent Stem Cells* / immunology
  • Induced Pluripotent Stem Cells* / metabolism
  • Interferon-beta / immunology
  • Interferon-beta / metabolism
  • Membrane Proteins* / metabolism
  • Mesenchymal Stem Cells* / immunology
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy
  • THP-1 Cells

Substances

  • Membrane Proteins
  • STING1 protein, human
  • Interferon-beta