• Role of STAT3 and gastric cancer stem cells in immunosuppressive tumor environment
  • Monireh Hajimoradi,1,*
    1. Department of Immunology, Razi Vaccine and Serum Research Institute, Agricultural Research, Education, and Extension Organization, Karaj, Iran


  • Introduction: Existence of Cancer Stem Cells (CSCs) in the tumor tissues confers resistancy of cancers to current therapeutic approaches and disease relapse. STAT3 (Signal Transducers and Activators of Transcription-3) transcription factor have been shown higher expression, activation and correlation with stemness properties of CSCs from gastric cancer and some others. With regard to immunosuppressive effects of cancer cells, We evaluate the possible role of STAT3 in conditions of tumor microenvironment.
  • Methods: We enriched CSCs from human gastric cancer cell lines MKN-45 and AGS based on spheroid formation and assessed the STAT3 activation using phospho flow cytometry, western blotting, immunoflourscent staining and intra nucleus localization. Q-RT-PCR used for STAT3, stemness and cytokine genes expression in spheroids derived cells and parental cells.
  • Results: Spheroids were identified as structures enriched for CSCs. Spheroid cells compared to the parental cells showed higher immunosuppressive effects on T lymphocyte proliferation, VEGF and TGF-β cytokine expression and regulatory T cell differentiation. Then demonstrate that STAT3 inhibition of cancer cells by Stattic small molecule further to diminish stemness properties including spheroid formation and pluripotency gene expression, decrease the immunosupression of cancer cells and shift Th17/Treg towards Th17.
  • Conclusion: These findings showed potent immunosuppression of CSCs may related to somewhat STAT3 activation .However, in vivo investigation of anti-tumoric and immunomodulatory effects of STAT3 inhibition is desirable. The present findings could be useful in therapeutical processes directing at CSCs and improve the tumor special niche.
  • Keywords: Cancer Stem Cells, Gastric Cancer, STAT3, immunosuppression