Immunotherapies and immune check-points

556 Background: Immune check points blockade with specific antibodies can accelerate anti-tumor immunity, resulting in a clinical response in patients with various types of cancer. Thus, a wide variety of treatment combinations based on PD-L1/ PD-1 pathway blockage are under development to enhance the therapeutic effect. Here, the effects of the combination treatment of PRI-724, a selective inhibitor of the CBP/β-catenin, with anti-PD-L1 antibody were examined in a mouse model of the liver metastasis of colon cancer. Methods: Mice were inoculated with SL4 colon cancer cells into the spleen to produce metastatic liver tumors. The animals were intraperitoneally injected with or without PRI-724 and/or anti-PD-L1 antibody (10F.9G2) 3 times a week. A part of mice treated with PRI-724 and anti-PD-L1 antibody was administrated with anti-mouse CD4 or CD8 antibody 3 times a week. First, to evaluate anti-tumor effect in those mice, we analyzed liver histology and survival rates after treatment. Next, to examine immune response in the liver, intrahepatic lymphocytes were analyzed by FACS for CD8 memory phenotype, Treg cells, macrophages, and dendritic cells, and the cytokine production from these cells (TNFa, IFNg etc.). Furthermore, inflammatory cytokines and chemokines mRNAs levels and PCR array concerned to Wnt signaling in the liver and serum cytokines levels were also analyzed. Results: The combination of the treatments resulted in regression of tumor growth, whereas monotherapy of each treatment did not show any anti-tumor activity. PRI-724 increased T lymphocytes recruitment, including CD8+ T cells, in the tumor, which may have been induced by inflammatory chemokines and a change of the macrophage property to the cytotoxic phenotype in the liver. Anti-PD-L1 antibody induced CD69+-activated T lymphocytes in the PRI-724-treated livers of mice inoculated with SL4. Administration of anti-CD8 antibody canceled the anti-tumor effects of the combination treatments of PRI-724 and anti-PD-L1 antibody. Conclusions: Targeting CBP/β-catenin combined with PD-1/PD-L1 immune check points blockade shows potential as a new therapeutic strategy for treating the liver metastasis of colon cancer.

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Current advances in kidney cancer immunotherapy

Cancer Urology ◽

10.17650/1726-9776-2019-15-4-30-38 ◽

2020 ◽

Vol 15 (4) ◽

pp. 30-38 ◽

Cited By ~ 2

Author(s):

A. A. Korotaeva ◽

N. V. Apanovich ◽

E. A. Braga ◽

V. B. Matveev ◽

A. V. Karpukhin

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Kidney Cancer ◽

Renal Cell ◽

Expression Profiles ◽

Control Point ◽

Malignant Neoplasms ◽

Immune Control ◽

Check Points ◽

Immune Check Points

In Russia, among tumors of the genitourinary system, renal cell carcinoma takes the 2nd place after prostate cancer. In 25 % of patients at the time of diagnosis, metastases are detected. Treatment of advanced stages of renal cell carcinoma is often not effective enough. The introduction into clinical practice of modern immunotherapeutic drugs based on inhibition of immune check points has changed the prognosis of the disease for many patients with various malignant neoplasms, including kidney cancer. In this article, we described the results of recent clinical trials on the use of immunotherapy in the treatment of kidney cancer. The most effective is combination of drugs that inhibit different immune check points, and a combination of a check point inhibitor with a targeted drug. This approach is likely to be a major one in the treatment of renal cell carcinoma in the short term. Combinations of control point inhibitors with radiation therapy and immunomodulatory drugs, the role of miRNAs in the regulation of expression of immune control points, the significance and characteristics of the microbiome in connection with the success of immunotherapy for kidney cancer, gene expression profiles as biomarkers of the immune response, and other biomarkers are considered. A better understanding of the mechanisms that limit the effectiveness of immune control point inhibitors will improve future treatment.

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ICOS enhances follicular T helper responses and deteriorates the pathogenic process of liver in mice infected with Schistosoma japonicum

10.1101/2020.02.27.968248 ◽

2020 ◽

Author(s):

Bo Wang ◽

Song Liang ◽

Yan-Yan Wang ◽

Yu Wang ◽

Chao-Ming Xia

Keyword(s):

Immune Responses ◽

Molecular Mechanisms ◽

Granulomatous Inflammation ◽

Liver Inflammation ◽

Humoral Immune ◽

Tfh Cells ◽

Humoral Immune Responses ◽

Cytokine Responses ◽

Check Points ◽

Immune Check Points

AbstractBackgroundHumoral immune responses play an important role in mediating liver granulomatous inflammation and fibrosis in schistosomiasis. Follicular helper T (Tfh) cells have a central role in mediating humoral immune responses. Generation of Tfh cells depends on inducible T cell costimulator (ICOS) signaling, but the underlying molecular mechanisms are incompletely understood in pathogenesis of schistosomiasis.Methodology/Principal FindingsWe used a strain of ICOS-transgenic (Tg) mice to test the degrees of liver granulomatous inflammation and fibrosis, the frequency of splenic Tfh cells and soluble egg antigen-specific cytokine responses longitudinally in mice following Schistosoma japonicum (S. japonicum) infection. In comparison with that in wide-type (WT) mice, significantly severer liver granulomatous inflammation and fibrosis and higher mortality were observed in ICOS-Tg mice. Significantly higher frequency of splenic Tfh cells was accompanied by significantly higher levels of Bcl-6 and CXCR5 expression in the livers of ICOS-Tg mice. Furthermore, significantly higher levels of SEA-specific IL-4, IL-6, IL-10, IL-13, IL-17A, IL-21 and TGF-β1 responses, but lower levels of IFN-γ responses were detected in ICOS-Tg mice, which were abrogated by treatment with ICOS blockers in vitro. In addition, significantly higher levels of serum anti-SEA IgG were detected in ICOS-Tg mice.Conclusions/SignificanceThe ICOS-related signaling may promote the pathogenesis of murine schistosomiasis by polarizing Tfh cells, which may be immune check points for the prevention and intervention of schistosomiasis.Author summaryGranulomatous inflammation and fibrosis in the liver are the major pathogenic characteristics of schistosomiasis. ICOS is crucial for the development of Tfh cells, which are the key modulators of B cell activation and humoral immunity. However, the underlying molecular mechanisms are incompletely understood in pathogenesis of schistosomiasis. Here, our results showed that the ICOS over-expression would significantly induce severer liver inflammation and fibrosis, higher frequency of splenic Tfh, higher levels of anti-SEA IgG as well as imbalanced SEA-specific cytokine responses in ICOS-Tg mice. The findings suggested that ICOS signaling may promote the pathogenesis of murine schistosoma-related liver inflammation and fibrosis by polarizing Tfh cells. Potentially, ICOS signaling and Tfh cells may be immune check points for the prevention and intervention of schistosomiasis.

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Problems of the preliminary customs informing system and the introduction of the Single Window at the sea check points of the Russian Federation

MATEC Web of Conferences ◽

10.1051/matecconf/201823904004 ◽

2018 ◽

Vol 239 ◽

pp. 04004 ◽

Cited By ~ 4

Author(s):

Svetlana Maydanova ◽

Igor Ilin

Keyword(s):

Developing Countries ◽

International Trade ◽

Russian Federation ◽

International Organizations ◽

International Standards ◽

Eurasian Economic Union ◽

Check Points ◽

The Russian Federation ◽

Economic Union ◽

National Governments

The Single Window concept in the international trade and logistics has been explored by international organizations and national governments over the last two decades. International standards and recommendations, government decisions on this approach are widespread today in both developed and developing countries. Similar decisions and legal acts were implemented during the last ten years by the Russian Federation, as a member of the Eurasian Economic Union. This article provides overview of the following coherent stage – the implementation of preliminary customs informing system at sea check points of the RF with concerns of the Single Window introduction.

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The Microstructure and Mechanical Properties of Ni-Based Superalloy after Service Exposure in Gas Turbine

Materials Science Forum ◽

10.4028/www.scientific.net/msf.654-656.2523 ◽

2010 ◽

Vol 654-656 ◽

pp. 2523-2526 ◽

Cited By ~ 2

Author(s):

Keun Bong Yoo ◽

Han Sang Lee

Keyword(s):

High Temperature ◽

Gas Turbine ◽

Mechanical Tests ◽

Time Dependent ◽

Second Stage ◽

Degradation Analysis ◽

Check Points ◽

Tcp Phase ◽

Service Exposure ◽

High Temperature Tensile

Many investigations about superalloys and coatings have been done in the laboratory, but evaluating the degradation condition of hot section components during service is still important not only for repair and reuse but also for outage prevention. Time dependent degradation for second stage blades of gas turbine was investigated. The degradation analysis for used blades was divided into microstructure changes by position of the blade and mechanical tests of high temperature tensile test. In the microstructure analysis, the rafting and coarsening of γ', MC decomposition and TCP phase formation occurred and progressed with increasing service time, and especially the leading and trailing edge of top layer should be a check points for used blade. High temperature tensile results of 25,000 and 52,000 hrs used blades were also compared with serviced time and position in each blade.

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WHY SOME YARROWIA LIPOLYTICA STRAINS SECRET CITRIC ACID TO THE MEDIUM?

Electronic Journal of Polish Agricultural Universities ◽

10.30825/5.ejpau.188.2020.23.3 ◽

2020 ◽

Vol 23 (3) ◽

Author(s):

Małgorzata Robak ◽

Keyword(s):

Citric Acid ◽

Metabolic Regulation ◽

Transport Systems ◽

Strain Development ◽

Future Studies ◽

Metabolism Regulation ◽

Starting Point ◽

Check Points ◽

Intracellular Ca ◽

Strain Dependent

Despite many studies, the “check points” of metabolic regulation of citric acid (CA) secretion by the yeasts Y.lipolytica still remain unknown. In this manuscript, some possible aspects of strain dependent secretion as well as CA metabolism regulation were discussed. Keys enzymes’ activities, substrate concentration, affinity of the uptake systems, intracellular CA concentration and strains abilities were the main points taken into consideration. The direction for the future studies emerged from this review, mainly connected to cellular and mitochondrial citrate transport systems and cellular substrates transporters (glucose, fructose, glycerol, ethanol and acetate), give promising starting point for future efficient strain development.

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ACCELERATION OF TOPOGRAPHIC MAP PRODUCTION USING SEMI-AUTOMATIC DTM FROM DSM RADAR DATA

ISPRS - International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences ◽

10.5194/isprs-archives-xli-b7-47-2016 ◽

2016 ◽

Vol XLI-B7 ◽

pp. 47-54

Author(s):

Aldino Rizaldy ◽

Ratna Mayasari

Keyword(s):

Conventional Method ◽

Point Cloud ◽

Radar Data ◽

Stereo Image ◽

Human Operator ◽

Topographic Map ◽

Tropical Area ◽

Check Points ◽

Map Scale ◽

Government Institution

Badan Informasi Geospasial (BIG) is government institution in Indonesia which is responsible to provide Topographic Map at several map scale. For medium map scale, e.g. 1:25.000 or 1:50.000, DSM from Radar data is very good solution since Radar is able to penetrate cloud that usually covering tropical area in Indonesia. DSM Radar is produced using Radargrammetry and Interferrometry technique. The conventional method of DTM production is using “stereo-mate”, the stereo image created from DSM Radar and ORRI (Ortho Rectified Radar Image), and human operator will digitizing masspoint and breakline manually using digital stereoplotter workstation. This technique is accurate but very costly and time consuming, also needs large resource of human operator. Since DSMs are already generated, it is possible to filter DSM to DTM using several techniques. This paper will study the possibility of DSM to DTM filtering using technique that usually used in point cloud LIDAR filtering. Accuracy of this method will also be calculated using enough numbers of check points. If the accuracy meets the requirement, this method is very potential to accelerate the production of Topographic Map in Indonesia.

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Check points of clothing design

The Japanese Journal of Ergonomics ◽

10.5100/jje.30.supplement_24 ◽

1994 ◽

Vol 30 (Supplement) ◽

pp. 24-25

Author(s):

Akio Shinozaki

Keyword(s):

Clothing Design ◽

Check Points

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Implantable vaccines: a solution for immune system manipulation to any antigenic stimulus

Journal of Immunological Sciences ◽

10.29245/2578-3009/2020/4.1193 ◽

2020 ◽

Vol 4 (4) ◽

pp. 5-11

Author(s):

Ioanna Zerva ◽

Vasileia Pateraki ◽

Irene Athanassakis

Keyword(s):

Immune Response ◽

Ex Vivo ◽

Great Majority ◽

Delivery Systems ◽

Antigen Delivery ◽

Immune Responsiveness ◽

Antigenic Stimulus ◽

Human Pathology ◽

Check Points ◽

Antigen Delivery Systems

Effective and side-effect-free vaccines are still difficult tasks to achieve for a great majority of antigenic stimuli. Pathogen manipulation to abort infectivity and antigen delivery to ensure immune responsiveness are the major components vaccine technology tries to resolve. However, the development of an immune response is still a complicated matter, lies on hundreds of parameters and any effort towards activation can easily lead to adverse effects, making immunotherapy very difficult to control. The present review attempts to highlight the major parameters affecting immune responsiveness and show that vaccine technology, except from pathogen manipulation and the development of antigen delivery systems, requires attention to additional check-points. Analyzing the recently described personalized implantable vaccine technology, it becomes obvious that the nature of each antigenic stimulus dictates different responsiveness to the organism, which discourages the use of universal adjuvant and antigen-delivery systems. On the contrary, the ex vivo tuning of the immune response proposed by the implantable vaccine technology, allows controllable amendment of the response. The development of personalized technologies is expected to provide valuable tools for the management of human pathology.

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ANALYSIS OF INFLUENCE OF TERRAIN RELIEF ROUGHNESS ON DEM ACCURACY GENERATED FROM LIDAR IN THE CZECH REPUBLIC TERRITORY

ISPRS - International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences ◽

10.5194/isprs-archives-xli-b4-25-2016 ◽

2016 ◽

Vol XLI-B4 ◽

pp. 25-30 ◽

Cited By ~ 1

Author(s):

M. Hubacek ◽

V. Kovarik ◽

V. Kratochvil

Keyword(s):

Czech Republic ◽

Laser Scanning ◽

Vegetation Coverage ◽

The Czech Republic ◽

Digital Elevation ◽

Lower Accuracy ◽

Check Points ◽

Elevation Data ◽

Dem Accuracy ◽

Elevation Model

Digital elevation models are today a common part of geographic information systems and derived applications. The way of their creation is varied. It depends on the extent of area, required accuracy, delivery time, financial resources and technologies available. The first model covering the whole territory of the Czech Republic was created already in the early 1980's. Currently, the 5th DEM generation is being finished. Data collection for this model was realized using the airborne laser scanning which allowed creating the DEM of a new generation having the precision up to a decimetre. Model of such a precision expands the possibilities of employing the DEM and it also offers new opportunities for the use of elevation data especially in a domain of modelling the phenomena dependent on highly accurate data. The examples are precise modelling of hydrological phenomena, studying micro-relief objects, modelling the vehicle movement, detecting and describing historical changes of a landscape, designing constructions etc. <br><br> Due to a nature of the technology used for collecting data and generating DEM, it is assumed that the resulting model achieves lower accuracy in areas covered by vegetation and in built-up areas. Therefore the verification of model accuracy was carried out in five selected areas in Moravia. The network of check points was established using a total station in each area. To determine the reference heights of check points, the known geodetic points whose heights were defined using levelling were used. Up to several thousands of points were surveyed in each area. Individual points were selected according to a different configuration of relief, different surface types, and different vegetation coverage. The sets of deviations were obtained by comparing the DEM 5G heights with reference heights which was followed by verification of tested elevation model. Results of the analysis showed that the model reaches generally higher precision than the declared one in majority of areas. This applies in particular to areas covered by vegetation. By contrast, the larger deviations occurred in relation to the slope of the terrain, in particular in the micro-relief objects. The results are presented in this article.

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