PURPOSE: Immune checkpoint inhibitors (ICIs) dramatically changed the prognosis of patients with NSCLC. Unfortunately, a reliable predictive biomarker is still missing. Commonly used biomarkers, such as PD-L1, MSI, or TMB, are not quite accurate in predicting ICI efficacy. METHODS: In this prospective observational cohort study, we investigated the predictive role of erythrocytes, thrombocytes, innate and adaptive immune cells, complement proteins (C3, C4), and cytokines from peripheral blood of 224 patients with stage III/IV NSCLC treated with ICI alone (pembrolizumab, nivolumab, and atezolizumab) or in combination (nivolumab + ipilimumab) with chemotherapy. These values were analyzed for associations with the response to the treatment and survival endpoints. RESULTS: Higher baseline Tregs, MPV, hemoglobin, and lower monocyte levels were associated with favorable PFS and OS. Moreover, increased baseline basophils and lower levels of C3 predicted significantly improved PFS. The levels of the baseline immature granulocytes, C3, and monocytes were significantly associated with the occurrence of partial regression at the first restaging. Multiple studied parameters (n = 9) were related to PFS benefit at the time of first restaging as compared to baseline values. In addition, PFS nonbenefit group showed a decrease in lymphocyte count after three months of therapy. The OS benefit was associated with higher levels of lymphocytes, erythrocytes, hemoglobin, MCV, and MPV, and a lower value of NLR after three months of treatment. CONCLUSION: Our work suggests that parameters from peripheral venous blood may be potential biomarkers in NSCLC patients on ICI. The baseline values of Tregs, C3, monocytes, and MPV are especially recommended for further investigation.

• Klíčová slova
• Biomarkers, Checkpoint inhibitors, Immunotherapy, NSCLC,
• MeSH
• antigeny CD274 MeSH
• biologické markery MeSH
• hemoglobiny terapeutické užití   MeSH
• imunofenotypizace MeSH
• inhibitory kontrolních bodů terapeutické užití   MeSH
• lidé MeSH
• nádory plic * MeSH
• nemalobuněčný karcinom plic * MeSH
• nivolumab terapeutické užití   MeSH
• prospektivní studie MeSH
• protinádorové látky imunologicky aktivní * terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• antigeny CD274 MeSH
• biologické markery MeSH
• hemoglobiny MeSH
• inhibitory kontrolních bodů MeSH
• nivolumab MeSH
• protinádorové látky imunologicky aktivní * MeSH

Ultra-small nanoparticles with sizes comparable to those of pores in the cellular membrane possess significant potential for application in the field of biomedicine. Silicon carbide ultra-small nanoparticles with varying surface termination were tested for the biological system represented by different human cells (using a human osteoblastic cell line as the reference system and a monocyte/macrophage cell line as immune cells). The three tested nanoparticle surface terminations resulted in the observation of different effects on cell metabolic activity. These effects were mostly noticeable in cases of monocytic cells, where each type of particle caused a completely different response ('as-prepared' particles, i.e., were highly cytotoxic, -OH terminated particles slightly increased the metabolic activity, while -NH2 terminated particles caused an almost doubled metabolic activity) after 24 h of incubation. Subsequently, the release of cytokines from such treated monocytes and their differentiation into activated cells was determined. The results revealed the potential modulation of immune cell behavior following stimulation with particular ultra-small nanoparticles, thus opening up new fields for novel silicon carbide nanoparticle biomedical applications.

• Klíčová slova
• cytotoxicity, immune cells, nanoparticles, osteoblasts, silicon carbide,
• Publikační typ
• časopisecké články MeSH

Our work examined the production of intracellular interferon (INF)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, and IL-4 by in vitro stimulated CD3+ cells from 38 chronic myeloid leukemia (CML) patients. At the time of diagnosis the percentages of cells producing INF-γ, TNF-α, and IL-2 were strongly suppressed compared to those in healthy control subjects. Hematological remission achieved through treatment with tyrosine-kinase inhibitors was associated with a highly significant increase in the ratio of cells producing all 4 cytokines. The percentages of CD3+ cells producing cytokines were dependent on age, more so in CML patients than in healthy controls, and they negatively correlated with the number of leukocytes. Patients with an optimal therapy outcome possessed higher percentages of cytokine-producing CD3+ cells at diagnosis than those with nonoptimal outcomes. This difference was statistically significant in the case of INF-γ-producing cells, and it was on the brink of significance in the case of IL-2-producing cells.

• Klíčová slova
• Chronic myeloid leukemia, Interferon-γ, Interleukin-2, Interleukin-4, Intracellular cytokine production, Tumor necrosis factor-α,
• MeSH
• antigeny CD3 metabolismus   MeSH
• chronická myeloidní leukemie farmakoterapie   imunologie   MeSH
• cytokiny biosyntéza   MeSH
• dospělí MeSH
• interferon gama biosyntéza   MeSH
• interleukin-2 biosyntéza   MeSH
• interleukin-4 biosyntéza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• T-lymfocyty imunologie   MeSH
• techniky in vitro MeSH
• TNF-alfa biosyntéza   MeSH
• tumor burden imunologie   MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD3 MeSH
• cytokiny MeSH
• IL2 protein, human MeSH Prohlížeč
• IL4 protein, human MeSH Prohlížeč
• interferon gama MeSH
• interleukin-2 MeSH
• interleukin-4 MeSH
• TNF protein, human MeSH Prohlížeč
• TNF-alfa MeSH

Serum samples taken at diagnosis in 28 chronic myeloid leukemia patients were tested for the presence of 20 cytokines by a magnetic bead-based Bio-plex immunoassay. According to complete cytogenetic remission achieved at 12 months of treatment, patients were divided into groups with either optimal or non-optimal outcome. Patients with increased cytokine levels tended to react optimally to the therapy more frequently than those others. TGF-β3 was a notable exception; its levels were significantly higher in patients with non-optimal outcomes. Further analysis enabled us to define two combinations of cytokine cut-off levels - namely low TGF-β3 and either high IL-8 or high MCP-1-each of which corresponded to therapy outcome better than either Sokal or EUTOS scores.

• Klíčová slova
• Chronic myeloid leukemia, EUTOS, Prediction reliability, Serum cytokines, Sokal,
• MeSH
• biologické markery MeSH
• chronická myeloidní leukemie krev   diagnóza   mortalita   terapie   MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• cytokiny MeSH

Indoleamine 2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan 2,3-dioxygenase (TDO) represent some of the key immune regulators. Their increased activity has been demonstrated in a number of human malignancies but not yet in chronic myeloid leukemia (CML). In the present study, the activity of these enzymes was tested in 29 CML patients and 28 healthy subjects by monitoring the kynurenine (KYN)/tryptophan ratio. Serum samples taken prior to the therapy displayed a highly significant difference in KYN levels between the patient and control groups. However, increased KYN levels were detected in only 13 (44.8%) of these CML patients. The KYN levels in pretreatment sera of the patients correlated with the tumor burden. There was also a strong correlation between KYN levels and uric acid levels (UA). This suggests but does not prove the possible involvement of UA in activating IDO family of enzymes. Whenever tested, the increased KYN levels normalized in the course of the therapy. Patients with normal KYN levels in their pretreatment sera and subsequently treated with interferon-α, showed a transitory increase in their KYN levels. The present data indicate that CML should be added to the malignancies with an increased activity of the IDO family of enzymes and suggest that IDO inhibitors may be used in the treatment of CML patients.

• Klíčová slova
• 3-dioxygenase, CML, chronic myeloid leukemia, IDO, indoleamine 2, 3-dioxygenase, INFα, interferon- α, INFγ, interferon-γ, KTI, kynurenine/tryptophan index, KYN, kynurenine, NK, natural killer, PBMC, peripheral blood mononuclear cells, Ph+, Philadelphia chromosome positive, T regs, regulatory T cells, TDO, tryptophan 2, 3-dioxygenase, TKI, tyrosine-kinase inhibitors, TRY, tryptophan, UA, uric acid., chronic myeloid leukemia, indoleamine 2, kynurenine, tryptophan metabolism, uric acid,
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Similarity among food allergens is a great problem affecting the specificity of diagnosis and treatment of allergic patients. We have observed that 80% of patients with food (including wheat) and pollen allergies have increased IgE antibodies against rice proteins. By immunoblotting, we documented that boiling decreased solubility and IgE reactivity of PBS-extracted rice and wheat proteins, yet in SDS extracts this reactivity was only slightly changed. The sera of patients highly positive on the IgE immunoblot and positive in basophil activation and skin prick test with boiled rice components were used for characterizing the IgE-binding proteins separated by 1D or 2D electrophoresis. Using mass spectrometry, we identified 22 rice SDS soluble proteins. Six of them were new thermostable potential rice allergens: glutelin C precursor, granule-bound starch synthase 1 protein, disulfide isomerase-like 1-1 protein, hypothetical protein OsI_13867, putative acid phosphatase precursor 1, and a protein encoded by locus Os02g0453600. All of the identified rice proteins differed from known wheat allergens, except proteins belonging to the α-amylase/trypsin inhibitor family. Furthermore, we would suggest that in patients with high IgE reactivity to wheat and rice components, the IgE immunoblot and skin prick test with boiled rice proteins could be beneficial before diet recommendation.

• MeSH
• bazofily imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• hmotnostní spektrometrie MeSH
• imunoblotting MeSH
• imunoglobulin E imunologie   MeSH
• kožní testy MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• potravinová alergie diagnóza   imunologie   MeSH
• předškolní dítě MeSH
• pšenice chemie   imunologie   MeSH
• rostlinné proteiny chemie   imunologie   MeSH
• rýže (rod) chemie   imunologie   MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• imunoglobulin E MeSH
• rostlinné proteiny MeSH

In the previous paper of ours we compared, prior to start any treatment, a number of immunological parameters in 24 chronic myeloid leukemia patients with the same number of healthy subjects matched by age and sex. We found significant differences in the levels of immunoglobulins, the C4 component of complement, the C-reactive protein, interleukin 6, the composition of lymphocyte population and the production of some cytokines by stimulated CD3+ cells. Eleven of these patients were followed longitudinally. After treatment with hydroxyurea, interferon alpha, imatinib mesylate and dasatinib, or various combinations thereof, hematological remission was achieved in all patients and complete cytogenetic remission in nine of them. There was a nearly general tendency towards normalization of the abnormalities observed in the patients at their enrollment.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• benzamidy MeSH
• C-reaktivní protein analýza   MeSH
• chronická myeloidní leukemie imunologie   terapie   MeSH
• dasatinib MeSH
• dospělí MeSH
• hydroxymočovina terapeutické užití   MeSH
• imatinib mesylát MeSH
• imunoglobuliny krev   MeSH
• imunologické faktory terapeutické užití   MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• interferon alfa terapeutické užití   MeSH
• interleukin-6 krev   MeSH
• komplement analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• piperaziny terapeutické užití   MeSH
• přirozená imunita * MeSH
• pyrimidiny terapeutické užití   MeSH
• T-lymfocyty metabolismus   MeSH
• thiazoly terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky MeSH
• benzamidy MeSH
• C-reaktivní protein MeSH
• dasatinib MeSH
• hydroxymočovina MeSH
• imatinib mesylát MeSH
• imunoglobuliny MeSH
• imunologické faktory MeSH
• inhibitory proteinkinas MeSH
• interferon alfa MeSH
• interleukin-6 MeSH
• komplement MeSH
• piperaziny MeSH
• pyrimidiny MeSH
• thiazoly MeSH

Vaccinia virus (VV) infects a broad range of host cells, and while it usually causes their lysis (i.e. necrosis), the nature of the cell-death phenomenon is not well understood. In this study, we show that VV induces apoptosis of cells of the murine macrophage line J774.G8, as revealed by morphological signs, DNA ladder formation, changes of mitochondrial membrane potential and annexin-V positivity. Apoptosis occurred in both untreated and IFN-gamma-pretreated macrophages, and could not be inhibited by aminoguanidine, a relatively specific inhibitor of inducible nitric oxide synthase. Inhibition of VV DNA synthesis and late gene expression by cytosine arabinoside also did not prevent apoptosis, while heat- or psoralen/UV-inactivated VV did not cause any apoptosis. Thus, VV early gene expression seems to be required for induction of apoptosis. At the cellular level, infection with VV induced a decrease in the levels of Bcl-x(L), an anti-apoptotic member of the Bcl-2 family. The importance of loss of Bcl-x(L) was demonstrated by prevention of VV-mediated apoptosis on expression of Bcl-2, a functional homologue of Bcl-x(L). Our findings provide evidence that induction of apoptosis by VV in macrophages requires virus early gene expression, does not involve nitric oxide, induces a decrease in mitochondrial membrane potential and is associated with altered levels of Bcl-x(L).

• MeSH
• antigeny virové MeSH
• apoptóza * MeSH
• buněčné linie MeSH
• guanidiny MeSH
• interferon gama farmakologie   MeSH
• makrofágy účinky léků   virologie   MeSH
• membránové potenciály MeSH
• mitochondrie fyziologie   MeSH
• myši MeSH
• protein bcl-X MeSH
• protein X asociovaný s bcl-2 MeSH
• protoonkogenní proteiny c-bcl-2 metabolismus   MeSH
• protoonkogenní proteiny metabolismus   MeSH
• signální transdukce * MeSH
• synthasa oxidu dusnatého, typ II MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   MeSH
• virion MeSH
• virové geny MeSH
• virus vakcinie fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny virové MeSH
• Bcl2l1 protein, mouse MeSH Prohlížeč
• guanidiny MeSH
• interferon gama MeSH
• Nos2 protein, mouse MeSH Prohlížeč
• pimagedine MeSH Prohlížeč
• protein bcl-X MeSH
• protein X asociovaný s bcl-2 MeSH
• protoonkogenní proteiny c-bcl-2 MeSH
• protoonkogenní proteiny MeSH
• synthasa oxidu dusnatého, typ II MeSH
• synthasa oxidu dusnatého MeSH