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

  • Cancer Lett. 2024 Jun 22:597:217081. doi: 10.1016/j.canlet.2024.217081.
Linxia Qian  1 ,  Zhonghan Zhang  2 ,  Ruhua Zhang  2 ,  Xueping Zheng  2 ,  Beibei Xiao  2 ,  Xiaomin Zhang  2 ,  Yuanzhong Wu  2 ,  Yang Chen  3 ,  Xingding Zhang  4 ,  Penghui Zhou  2 ,  Qingling Fu  5 ,  Tiebang Kang  6 ,  Ying Gao  7
Affiliations
  • 1. State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China; School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China.
  • 2. State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
  • 3. Departments of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, 510000, Guangdong, China.
  • 4. School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China.
  • 5. Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China. Electronic address: [email protected].
  • 6. State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China. Electronic address: [email protected].
  • 7. State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China. Electronic address: [email protected].
PMID: 38909776 DOI: 10.1016/j.canlet.2024.217081
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.
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