IMMU-40. ROLE OF HUMAN-β-DEFENSIN 3 IN GLIOBLASTOMA MULTIFORME
Year: 2017
Type: conference-abstract
Abstract: Glioblastoma multiforme (GBM) is the most common primary brain tumor with current therapies offering only palliative benefit. Cellular hierarchy in GBM is maintained by the presence of cancer stem cells (CSCs), which have the capability for self-renewal and proliferation. We investigated the immunomodulatory effects of the cancer stem cell-niche by examining the secretion of defensins – specifically human b-defensin 3 (hBD-3) - and their interactions with macrophages and microglia. Immunohistochemistry of primary tumor sections revealed the presence of hBD-3 in the tumor periphery. Co-localization of hBD-3 with stem cell markers Sox2 and Nestin demonstrates that the hBD-3 expressing cells were CSCs. IHC also revealed the presence of CD68+ macrophages alongside HBD-3 expressing Sox2+ CSCs. CSCs were isolated from primary GBM tumors by FACS using CD15 and CD133 as markers. QT-PCR revealed an increase in the expression of HBD-3 in purified CSCs compared to control hNSCs cell lines. Peripherally derived MDSCs from patients with primary GBM did not express hBD-3. Chemotaxis assays indicate the ability of recombinant hBD-3 to chemoattract macrophages and microglia associated with GBM. HBD-3 is secreted by cancer stem cells and plays a role in immunomodulation. The ability of hBD-3 to attract macrophages suggests that it may play a role in the M1 to M2 phenotype switch of macrophages – thereby allowing for immune evasion. Future experiments include blocking myeloid cell expressing chemotactic receptors to determine their role in hBD-3 mediated chemotaxis. Additionally, in vivo shRNA experiments to knock down hBD-3 expression by CSCs in murine models of GBM will be done to definitively show its role in GBM immunomodulation. Understanding the role of immune cells in the tumor microenvironment is essential for development of new therapies for treatment of GBM.
Source: Neuro-Oncology
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2767819540