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Updated: Sep 24, 2025
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Infiltrating natural killer cells bind, lyse and increase chemotherapy efficacy in glioblastoma stem-like
Barbara Breznik1,2, Meng-Wei Ko3, Christopher Tse4
1Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, University of California School of Dentistry, 10833 Le Conte Ave, Los Angeles, CA, 90095, USA. barbara.breznik@nib.si.
Abstract:
Glioblastomas remain the most lethal primary brain tumors. Natural killer (NK) cell-based therapy is a promising immunotherapeutic strategy in the treatment of glioblastomas, since these cells can select and lyse therapy-resistant glioblastoma stem-like cells (GSLCs). Immunotherapy with super-charged NK cells has a potential as antitumor approach since we found their efficiency to kill patient-derived GSLCs in 2D and 3D models, potentially reversing the immunosuppression also seen in the patients. In addition to their potent cytotoxicity, NK cells secrete IFN-γ, upregulate GSLC surface expression of CD54 and MHC class I and increase sensitivity of GSLCs to chemotherapeutic drugs. Moreover, NK cell localization in peri-vascular regions in glioblastoma tissues and their close contact with GSLCs in tumorospheres suggests their ability to infiltrate glioblastoma tumors and target GSLCs. Due to GSLC heterogeneity and plasticity in regards to their stage of differentiation personalized immunotherapeutic strategies should be designed to effectively target glioblastomas.
Insights
Natural killer (NK) cell therapy shows promise against glioblastomas by targeting therapy-resistant glioblastoma stem-like cells (GSLCs). Super-charged NK cells enhance glioblastoma treatment by increasing tumor cell death and drug sensitivity.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Therapy
Background:
- Glioblastomas are aggressive primary brain tumors with poor prognosis.
- Glioblastoma stem-like cells (GSLCs) contribute to tumor resistance and recurrence.
- Natural killer (NK) cells are immune cells with potential for cancer immunotherapy.
Purpose of the Study:
- To evaluate the efficacy of NK cell-based immunotherapy against glioblastoma.
- To investigate the mechanisms by which NK cells target and eliminate GSLCs.
- To explore the potential of super-charged NK cells in glioblastoma treatment.
Main Methods:
- Utilized patient-derived glioblastoma stem-like cells (GSLCs) in 2D and 3D culture models.
- Assessed NK cell cytotoxicity against GSLCs.
- Analyzed NK cell-mediated modulation of GSLC surface markers (CD54, MHC class I) and cytokine secretion (IFN-γ).
- Investigated NK cell infiltration and localization within glioblastoma tissue models.
Main Results:
- NK cells demonstrated potent cytotoxicity against patient-derived GSLCs in vitro.
- Super-charged NK cells effectively killed GSLCs and showed potential to reverse tumor immunosuppression.
- NK cells increased GSLC sensitivity to chemotherapeutic drugs.
- NK cells secreted IFN-γ and upregulated CD54 and MHC class I on GSLCs.
- NK cells were observed in perivascular regions and in close contact with GSLCs in tumor models, suggesting infiltration capacity.
Conclusions:
- NK cell-based immunotherapy is a promising strategy for glioblastoma treatment, particularly targeting therapy-resistant GSLCs.
- Super-charged NK cells offer enhanced anti-glioblastoma activity and could overcome tumor immunosuppression.
- NK cells modulate the tumor microenvironment and enhance the efficacy of conventional therapies.
- Personalized immunotherapeutic strategies are necessary due to the heterogeneity of GSLCs for effective glioblastoma targeting.
