Glioma cancer stem cells modulating the local tumor immune environment

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KHAN I., Mahfooz S., KARAÇAM B., ELBASAN E. B., Akdur K., Karimi H., ...More

FRONTIERS IN MOLECULAR NEUROSCIENCE, vol.15, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 15
  • Publication Date: 2022
  • Doi Number: 10.3389/fnmol.2022.1029657
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, Directory of Open Access Journals
  • Keywords: glioma stem cells, glioblastoma, tumor immune response, systemic immune response, tumor microenvironment, GROWTH-FACTOR, FAS-LIGAND, BRAIN, LYMPHOCYTES, EXPRESSION, INVOLVEMENT, MECHANISMS, MICROGLIA, REGULATOR, CD4(+)
  • Bezmialem Vakıf University Affiliated: Yes


Glioma stem cells (GSCs) drive the resistance mechanism in glioma tumors and mediate the suppression of innate and adaptive immune responses. Here we investigate the expression of mesenchymal-epithelial transition factor (c-Met) and Fas receptor in GSCs and their role in potentiating the tumor-mediated immune suppression through modulation of tumor infiltrating lymphocyte (TIL) population. Tumor tissues were collected from 4 patients who underwent surgery for glioblastoma. GSCs were cultured as neurospheres and evaluated for the co-expression of CD133, c-Met and FasL through flow cytometry. TILs were isolated and evaluated for the lymphocyte subset frequencies including CD3 +, CD4 +, CD8 +, regulatory T cells (FOXP3 + CD25) and microglia (CD11b + CD45) using flow cytometry. Our findings revealed that a significant population of GSCs in all four samples expressed c-Met (89-99%) and FasL (73-97%). A significantly low microglia population was found in local immune cells ranging from 3 to 5%. We did not find a statistically significant correlation between expressions of c-Met + GSC and FasL + GSC with local and systemic immune cells. This may be regarded to the small sample size. The percent c-Met + and FasL + GSC population appeared to be related to percent cytotoxic T cells, regulatory T cells and microglia populations in glioblastoma patients. Further investigation is warranted in a larger sample size.