Determining the role of NSC-derived EVs in glioblastoma progression and resistance to CIK cell immunotherapy

Dr. Giedrius Steponaitis

Glioblastoma (GBM, grade IV) is a highly aggressive and incurable brain cancer with an average survival time of 15 months. Emerging evidence suggests that neural stem cells (NSCs) in the subventricular zone of the brain are the key cells responsible for the development of GBM (PMID:37109434) and may also be involved in GBM relapse and treatment resistance. The interaction between NSCs and GBM is apparent from studies showing that GBM-derived extracellular vesicles (EVs) can alter the phenotype and biological behavior of NSCs in vitro (PMID:31521694). Since EVs are released by all cell types, including NSCs, they are known to be involved in intercellular communication. On top of that, NSC-derived extracellular vesicles (NSC-EVs) are able to modulate the local nervous system microenvironment and distant neuronal functions. Considering this, in the current proposal, we sought to investigate 1) whether NSC-EVs can inhibit or promote the growth of GBM cells, 2) whether NSC-EVs have an affinity to impair the immunomodulatory function of immune cells (T/NKT cells) targeting GBM proliferation.

• To investigate this, we will first employ advanced and established techniques to isolate NSC-derived EVs and assess their effects on the proliferation and migration of preclinical GBM cells model (patient-derived primary GBM cells). Our experimental setup mimics the CNS microenvironment in which cell populations communicate with each other and will allow us to collect secretions associated with NSC-derived EVs (e.g. miRNAs) in response to cancer cells.
• Next, we will determine whether NSC-derived EVs could synergistically enhance the antitumor capacity of cytokine-induced killer cells (CIK cells: T/NKT cell types), an adoptive cancer immunotherapy which is already in use for GBM patients in the clinic (PMID:35463313).

This will be the first comprehensive study to characterize the molecular content and functional role of NSC-derived EVs in GBM progression and resistance to adoptive cellular immunotherapy.

• A public event primarily intended for the scientific community due to its content specificity but also open to the general public: A Seminar-type lecture on the Cancer-EVs axis at the University Hospital Bonn by researchers from Lithuania (LSMU). Date: September 2025
• A public event primarily intended for the scientific community due to its content specificity but also open to the general public: A Seminar-type lecture at Lithuanian University of Health Sciences, Neuroscience Institute by researcher prof. dr. Amit Sharma (UKB, Germany). Date: October 2025

Direct: Researcher in the field of molecular neurooncology, and molecular immunology – 7 people

Indirect: Researcher at LSMU neuroscience institute, PhD students; Master and bachelor students; The personnel of International Relations and Study Centre – 20 people total