IMMUNE RESPONSE IN MALIGNANT GLIOMA

Objective: Malignant gliomas are primary brain tumors with excessive mortality and high resistance to chemotherapy and radiotherapy. The survival time for glioblastoma multi­forme is about 6-12 months. As key pathogenetic mechanisms are recognized the massive necrosis, angiogenesis and hypoxia within the tumor, as well as the resistance to apoptosis. It is also suspected that altered immune response might contribute to the fatal clinical outcome.The aim of the present study was to determine the immune status of patients with malignant gliomas.Material and methods: Peripheral blood lymphocytes were collected preoperatively from 9 patients (aged 57-76) diagnosed as anaplastic astrocytoma grade III (n=4) and glioblastoma multiforme (n=5). The following lymphocyte populations were analyzed by flow cytometry: CD19+, CD3+, CD3+CD4+, CD3+CD8+, CD3-CD56+, CD3+CD56+, CD3+CD25+, CD8-CD11b+, CD8+CD11b+, CD8+CD11b-. The results obtained were compared to reference values for each cell population.Results: No significant alterations were detected in CD19+, CD3+, CD3+CD4+, CD3+CD8+ cells, but the CD4/CD8 ratio was below the reference range in some cases. No obvious decrease in (CD3-CD56+) NK cells and (CD3-CD56+) NKT cells was observed in most patients. A reproducible phenomenon of increased CD8+CD11b+ and decreased CD8+CD11b- cells was noticed. These preliminary results suggest that the immune response in patients with malignant glioma is seriously disregulated. The rapid clinical deterioration, relapses and high mortality could be at least partially explained with the suppressed activity of NK-cells which are the major cytotoxic antitumoral cells. The increase in the population of activated suppressor-effector cells also contributes to the unfavourable outcome in malignant brain tumors.Conclusion: This pilot study reveals the presence of altered immune response in malignant gliomas and opens possibilities for prospective investigations concerning immune status and clinical outcome

Pro-Tumor and Anti-Tumor Functions of IL-17 and of TH17 Cells in Tumor Microenvironment

The current review reveals the seven subclasses of CD4+ T helper cells, i.e. Th1, Th2, Th9, Th17, Th22, regulatory T cells and Tfh, the cytokines produced by them and their role in tumor microenvironment. Main attention was paid to IL-17 and Th17 cells. IL-17-producing cells were described, among which were Treg17 cells and Tc17 cells. The transcription factors, engaged in the activation of Th17 cell differentiation were reviewed. It was shown that Th17 cells might possess regulatory functions in tumor microenvironments that directs toward immunosuppression. The reciprocity between Treg and Th17 cells is realized when the production of a large amount of TGF-β in tumors causes Treg cell differentiation, and the addition of IL-6 shifts the differentiation of naïve T cells to Th17 cells. The main pro-tumor role of IL-17 is the promotion of tumor angiogenesis through stimulation of fibroblasts and endothelial cells. The antitumor functions of IL-17 are associated with enhancement of cytotoxic activity of tumor specific CTL cells and with angiogenesis that provide channels through which immune cells might invade tumor and promote antitumor immunity

Adsorption of the Linear Poly(ethyleneimine) Precursor Poly(2-ethyl-2-oxazoline) and Sodium Dodecyl Sulfate Mixtures at the Air–Water Interface: The Impact of Modification of the Poly(ethyleneimine) Functionality

The adsorption of the polymer–surfactant mixture of poly­(2-ethyl-2-oxazoline)–sodium dodecyl sulfate at the air–water interface has been studied by neutron reflectivity and surface tension. The observed patterns of adsorption more closely resemble those encountered in weakly interacting polymer–surfactant mixtures, rather than the pronounced enhancements in adsorption observed in strongly interacting polymer–surfactant mixtures, such as in the related poly­(ethyleneimine)–sodium dodecyl sulfate mixtures. The adsorption was found to be strongly dependent on solution pH, polymer molecular weight, and polymer concentration. At the lower and higher molecular weights studied, there was little enhancement in the sodium dodecyl sulfate adsorption at low sodium dodecyl sulfate concentrations, whereas at the intermediate polymer molecular weights, some enhancement in the adsorption was observed. For the higher-molecular-weight polymers and at increasingly higher polymer concentrations, a significant reduction of the surfactant at the interface compared to pure sodium dodecyl sulfate occurred for sodium dodecyl sulfate concentrations between the critical aggregation concentration and the critical micellar concentration. The results illustrate the important role of modifying the functionality of poly­(ethyleneimine) on surface adsorption

Effect of Polymer Molecular Weight and Solution pH on the Surface Properties of Sodium Dodecylsulfate-Poly(Ethyleneimine) Mixtures

The effect of polymer molecular weight and solution pH on the surface properties of the anionic surfactant sodium dodecylsulfate, SDS, and a range of small linear poly­(ethyleneimine), PEI, polyelectrolytes of different molecular weights has been studied by surface tension, ST, and neutron reflectivity, NR, at the air–solution interface. The strong SDS–PEI interaction gives rise to a complex pattern of ST behavior which depends significantly on solution pH and PEI molecular weight. The ST data correlate broadly with the more direct determination of the surface adsorption and surface structure obtained using NR. At pH 3, 7, and 10, the strong SDS–PEI interaction results in a pronounced SDS adsorption at relatively low SDS and PEI concentrations, and is largely independent of pH and PEI molecular weight (for PEI molecular weights on the order of 320, 640, and 2000 Da). At pH 7 and 10, there are combinations of SDS and PEI concentrations for which surface multilayer structures form. For the PEI molecular weights of 320 and 640 Da, these surface multilayer structures are most well-developed at pH 10 and less so at pH 7. At the molecular weight of 2000 Da, they are poorly developed at both pH 7 and 10. This evolution in the surface structure with molecular weight is consistent with previous studies, where for a molecular weight of 25 000 Da no multilayer structures were observed for the linear PEI. The results show the importance with increasing polymer molecular weight of the entropic contribution due to the polymer flexibility in control of the surface multilayer formation

Solution pH and Oligoamine Molecular Weight Dependence of the Transition from Monolayer to Multilayer Adsorption at the Air–Water Interface from Sodium Dodecyl Sulfate/Oligoamine Mixtures

Neutron reflectivity and surface tension have been used to investigate the solution pH and oligoamine molecular weight dependence of the adsorption of sodium dodecyl sulfate (SDS)/oligoamine mixtures at the air–water interface. For diethylenetriamine, triamine, or triethylenetetramine, tetramine mixed with SDS, there is monolayer adsorption at pH 7 and 10, and multilayer adsorption at pH 3. For the slightly higher molecular weight tetraethylenepentamine, pentamine, and pentaethylenehexamine, hexamine, the adsorption is in the form of a monolayer at pH 3 and multilayers at pH 7 and 10. Hence, there is a pH driven transition from monolayer to multilayer adsorption, which shifts from low pH to higher pH as the oligoamine molecular weight increases from tetramine to pentamine. This results from the relative balance between the electrostatic attraction between the SDS and amine nitrogen group which decreases as the charge density decreases with increasing pH, the ion–dipole interaction between the amine nitrogen and SDS sulfate group which is dominant at higher pH, and the hydrophobic interalkyl chain interaction between bound SDS molecules which changes with oligoamine molecular weight

Effect of Architecture on the Formation of Surface Multilayer Structures at the Air–Solution Interface from Mixtures of Surfactant with Small Poly(ethyleneimine)s

The impact of ethyleneimine architecture on the adsorption behavior of mixtures of small poly­(ethyleneimines) and oligoethyleneimines (OEIs) with the anionic surfactant sodium dodecylsulfate (SDS) at the air–solution interface has been studied by surface tension (ST) and neutron reflectivity (NR). The strong surface interaction between OEI and SDS gives rise to complex surface tension behavior that has a pronounced pH dependence. The NR data provide more direct access to the surface structure and show that the patterns of ST behavior are correlated with substantial OEI/SDS adsorption and the spontaneous formation of surface multilayer structures. The regions of surface multilayer formation depend upon SDS and OEI concentrations, on the solution pH, and on the OEI architecture, linear or branched. For the linear OEIs (octaethyleneimine, linear poly­(ethyleneimine) or LPEI₈, and decaethyleneimine, LPEI₁₀) with SDS, surface multilayer formation occurs over a range of OEI and SDS concentrations at pH 7 and to a much lesser extent at pH 10, whereas at pH 3 only monolayer adsorption occurs. In contrast, for branched OEIs BPEI₈ and BPEI₁₀ surface multilayer formation occurs over a wide range of OEI and SDS concentrations at pH 3 and 7, and at pH 10, the adsorption is mainly in the form of a monolayer. The results provide important insight into how the OEI architecture and pH can be used to control and manipulate the nature of the OEI/surfactant adsorption