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Gamma-delta (γδ) T cells are innate immunity effector lymphocytes with known prominent anti-tumor reactivity against aggressive glioblastoma (GBM). However, therapeutic approaches have had limited success due to the protective blood-brain-barrier and the immunosuppressive GBM tumor microenvironment. In this study, we determined Vδ1 a Vδ2 γδ T cell populations in peripheral blood and paired tumor tissue samples in patients (n=40) following the resection and throughtout the therapy follow-up. Tumor samples were processed using enzymatic kits and gentleMACSTM Dissociator (Miltenyi Biotec Inc.) and tumor-infiltrating γδ T lymphocytes (TILs) were analyzed by flow cytometry.We found infiltration of both intratumoral CD3+ γδ T cell subsets in 68% tumor samples. We detected Vδ1 γδ T cells in the range 0-0.8% (median 0.26%). Majority of GBM patients presented the Vδ2 subset among TILs in the range 0-13.8% (median 1.5%). Functional studies showed prominent cytotoxicity of magnetically sorted Vδ1 a Vδ2 γδ T cells against GBM cell lines and more importantly against primary tumors. Detailed phenotypic profiling and single-cell sequencing of Vδ2 γδ T cells is currently underway. Next, we identified the EphA2 receptor as one of the targets for tumor-reactive Vδ1 γδ T cells. Specifically, we found that blocking of EphA2 expression resulted in significant inhibition of GBM killing mediated by Vδ1 γδ T cells. Furthermore, Luminex xMAP technology identified significantly elevated levels of stress ligand MICA and check-point inhibitor ligands PD-L1 (B7-H1, CD274) and B7-H3 (CD276) and galectin-9 in patients‘ plasma samples at diagnosis compared to age-matched controls.The patient’s clinical course and therapeutic protocols will be discussed.This study was supported by Ministry of Health, Czech Republic (grant NV19-05-00410 to AK) by Ministry of Health, Czech Republic-conceptual development of research organization (FNBr, 65269705). All rights reserved.

Pocet pacientek dosahujicich reprodukcniho věku a planujicich těhotenstvi diky pokroku v lecbě hydrocefalu pozvolna narůsta. Cetne změny v organizmu matky se podileji na zvýsene incidenci komplikaci během gravidity a porodu. Z těchto důvodů je nutne řadne prekoncepcni vysetřeni a stanoveni optimalniho sledovani těhotenstvi, vhodneho způsobu vedeni porodu a řeseni připadných komplikaci. Nezbytne je připadnou malfunkci shuntu spravně a vcas diagnostikovat a řesit ji individualně s přihlednutim k celkovemu a neurologickemu stavu pacientky a gestacnimu staři. Vaginalni porod je považovan větsinou autorů za prvni volbu. U pacientek s obstrukcnim hydrocefalem nebo při dramatickem průběhu malfunkce je provedeni primarniho cisařskeho řezu bezpecnějsi. Anestezie je možna epiduralni nebo celkova, připadně spinalni.

The possible role of immune-modulatory nonclassical molecules HLA-G and HLA-E in an anti-tumoral response and development of glioblastoma is not well characterized. In this study, we evaluated an expression of HLA-G and HLA-E by activated tumor infiltrating microglia/macrophages. We found production of HLA-G and HLA-E by tumor infiltrating activated microglia/macrophages in a majority of glioblastomas. We speculate that the expression of these molecules by activated microglia/CNS macrophages plays a role in the anti-tumoral immunity in the development of glioblastoma. Mechanisms of microglia–glioblastoma cell interactions with respect to the expression of these molecules deserves further study.

The role of nonclassical human leukocyte antigens G and E (HLA-G and HLA-E) was originally thought to be restricted to the protection of the fetus from a maternal allorecognition. Now it is known that HLA-G and HLA-E exert multiple immunoregulatory functions. A prognostic significance of the expression of HLA-G and HLA-E by neoplastic cells in glioblastoma is not well characterized. In this study, we evaluated the expression of HLA-G and HLA-E by neoplastic cells in 39 cases of glioblastoma. We found the production of HLA-G and HLA in a majority of cases. There was an unexpected positive correlation between the expression of HLA-E and length of survival. We speculate that the expression of this molecule by neoplastic cells may represent a coincidental selective pro-host advantage related to better response to subsequent therapeutic modalities. Mechanisms of glioblastoma cell pathophysiology and mechanisms of responses to therapeutic interventions in respect to the expression of these molecules deserves further study.

In addition to correct indications we emphasize the necessaity of correct operative technique with sufficient bone decompression, dural decompression with duroplasty, and later, the restoration of normal cerebrospinal fluid circulation by the release of arachnoid adhesions.