Infiltrating natural killer cells bind, lyse and increase chemotherapy efficacy in glioblastoma stem-like tumorospheres.
Barbara BreznikMeng-Wei KoChristopher TsePo-Chun ChenEmanuela SenjorBernarda MajcAnamarija HabičNicolas AngelillisMetka NovakVera ŽupunskiJernej MlakarDavid NathansonAnahid JewettPublished in: Communications biology (2022)
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.
Keyphrases
- nk cells
- end stage renal disease
- natural killer cells
- chronic kidney disease
- newly diagnosed
- ejection fraction
- induced apoptosis
- poor prognosis
- gene expression
- prognostic factors
- peritoneal dialysis
- squamous cell carcinoma
- stem cells
- immune response
- radiation therapy
- signaling pathway
- cell therapy
- oxidative stress
- long non coding rna
- mesenchymal stem cells
- replacement therapy