#CXCR3 antibody
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Boster Bio Anti-CXCR3 Antibody Picoband™ catalog # PB9079. Tested in IHC, WB applications. This antibody (CXCR3 antibody) reacts with Human, Rat.
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Check out this 5-star review on Biocompare and see how one researcher is using our anti-CXCR3 antibody in their plasma cell studies: https://tinyurl.com/y3lts6kq
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BioAdvisers said on Biotech Advisers
Dialogue between laboratory experts and experimental rookies
Experimental rookies: When I first entered the laboratory, it was completely a rookie. The boss first asked the literature to read the information, which was a bit confusing. Moreover, there are so many reagents in the literature, as well as recombinant proteins such as cytokines. The difference?
Laboratory experts: Recombinant protein is simply a protein obtained using DNA recombination technology; cytokines are small protein molecules secreted by cells that can induce various physiological reactions such as cell proliferation, growth or differentiation. In fact, they are also obtained using recombinant methods, which are recombinant Part of the protein. However, cytokines include many types, such as immune system regulators such as interleukins and interferons, growth factors such as fibroblast growth factor FGF, vascular endothelial growth factor VEGF, and chemokines such as CCL2 and CXCL8 (chemokine-induced cells Migration or chemotaxis).
Experimental rookies: Oh, that’s what it is. Learn today. But I just checked a factor I will use online, there are so many products on the market, how to choose the most suitable product from it, my choice difficulty syndrome is guilty, what should I do? What are the sources of protein products?
Laboratory experts: The most commonly used protein expression systems are mammalian cell expression system and E. coli expression system, in addition to yeast expression system and insect expression system. Some proteins require post-translational modifications to be biologically active. Mammalian cells can provide such modifications, but bacterial cells often cannot. Therefore, when purchasing this type of protein, you should pay special attention to the protein source in the product manual.
Experimental rookies: How do I choose these four expression systems? I suddenly felt a little lack of knowledge, and you need to be able to give pointers!
Laboratory experts: Do not dare to give pointers, but everyone can learn together. Before choosing an expression system, we need to fully understand our research objectives and select the most suitable expression system according to our application. The following table can be used as a reference.
Experimental rookies: I think the cytokines bought by the sister next door are powdered, so strange!
Laboratory experts: The recombinant protein products on the market are basically in the form of lyophilized powder. Only a small amount of the finished product is liquid, and the lyophilized powder is easier to transport and store.
Experimental rookies: How to determine the concentration of added cytokines during the experiment?
Laboratory experts: Since each manufacturer has different production processes or live measurement methods, the activity of cytokines is also different, so the recommended concentration of cytokines can refer to relevant literature or do concentration gradient experiments to determine the best concentration for your own experiments .
Experimental rookies: The molecular weight shown on the gel charts on many cytokine websites is very different from the theoretical molecular weight. What is the reason?
Laboratory experts: First of all, we need to understand two concepts: theoretical molecular weight and apparent molecular weight. The theoretical molecular weight is actually calculated based on the amino acid sequence of the protein; the apparent molecular weight is the protein molecular weight estimated by SDS polyacrylamide gel electrophoresis using a standard reference material of known molecular weight. We all know that the difference between the theoretical molecular weight and the apparent molecular weight is very common in the experiment. The molecular weight of the two on many websites is very different. A large part of it is due to the structure of the protein itself such as protein glycosylation.
Experimental rookies: How to choose the cytokine with good quality?
Laboratory experts: The influence of cytokines on the experiment cannot be underestimated. Once the selection fails, the experiment will not be carried out smoothly, wasting time and effort, so it is very important to choose a cytokine supplier with guaranteed quality. When we choose suppliers, we generally choose companies with good reputation, because companies with good reputation will carry out various quality control on their protein products to ensure the quality of the protein and the experimental effect. It is recommended to read the instructions carefully before purchasing, on the one hand, you can understand the basic information of the protein, on the other hand, the instruction manual will also provide a variety of data such as protein purity, endotoxin content, SDS-PAGE gel map. Of course, biological activity is also a factor to consider when choosing protein products. For example, BaF3 mouse pro-B cells transfected with human CXCR3 were treated with chemokine CCL10 to measure the chemotactic ability of CCL10; TGF-beta 1 was used to inhibit IL-4 induced HT-2 cell proliferation To detect the biological activity of TGF-beta 1.
Product NO Product Name PRP1012 Human IL-6 protein PRP1013 Human TNF-alpha protein PRP1010 Human bFGF protein, His Tag PRP1011 Mouse bFGF protein, His Tag PRP1014 Human IFN-gamma protein, His Tag PRP1015 Mouse IFN-gamma protein, His Tag
Abbkine’s cytokines have high quality guarantee:
Cell-based biological activity assay.
Complete quality control system.
Low endotoxin levels.
High purity,> 95%.
Lyophilized powder form.
Abbkine specializes in the fields of proteinology and cytology, and is committed to innovating and developing various antibodies, proteins, analytical reagents and kits, with a view to becoming a key promoter in the fields of life science research and development, drug research and development. We provide you with the favorite products of protein and immunological research users, from basic immunological products, such as protein extraction and quantification, to the internal reference labeling antibodies, primary antibodies and secondary antibodies of immunological experiments, etc .; the favorite products of cell research users, from Dyes and kits for detecting the state of cells, kits for extracting organelles, staining and tracking of cell substructures and cell metabolism detection products, and cytokine and protein detection kits for cell culture, only to help your research career !
About Abbkine
Our position: Serve global users of cell and protein research, and provide users with economical and technical product solutions through application processes and product portfolios.
Our mission: to stimulate our inner creativity, provide competitive biomedical products and services, and continue to create maximum value for customers.
Our vision: to be a respected, world-class supplier of biomedical products and services.
0 notes
Text
Bioadvisers shared on Biotech Advisers
Dialogue between laboratory experts and experimental rookies
Experimental rookies: When I first entered the laboratory, it was completely a rookie. The boss first asked the literature to read the information, which was a bit confusing. Moreover, there are so many reagents in the literature, as well as recombinant proteins such as cytokines. The difference?
Laboratory experts: Recombinant protein is simply a protein obtained using DNA recombination technology; cytokines are small protein molecules secreted by cells that can induce various physiological reactions such as cell proliferation, growth or differentiation. In fact, they are also obtained using recombinant methods, which are recombinant Part of the protein. However, cytokines include many types, such as immune system regulators such as interleukins and interferons, growth factors such as fibroblast growth factor FGF, vascular endothelial growth factor VEGF, and chemokines such as CCL2 and CXCL8 (chemokine-induced cells Migration or chemotaxis).
Experimental rookies: Oh, that’s what it is. Learn today. But I just checked a factor I will use online, there are so many products on the market, how to choose the most suitable product from it, my choice difficulty syndrome is guilty, what should I do? What are the sources of protein products?
Laboratory experts: The most commonly used protein expression systems are mammalian cell expression system and E. coli expression system, in addition to yeast expression system and insect expression system. Some proteins require post-translational modifications to be biologically active. Mammalian cells can provide such modifications, but bacterial cells often cannot. Therefore, when purchasing this type of protein, you should pay special attention to the protein source in the product manual.
Experimental rookies: How do I choose these four expression systems? I suddenly felt a little lack of knowledge, and you need to be able to give pointers!
Laboratory experts: Do not dare to give pointers, but everyone can learn together. Before choosing an expression system, we need to fully understand our research objectives and select the most suitable expression system according to our application. The following table can be used as a reference.
Experimental rookies: I think the cytokines bought by the sister next door are powdered, so strange!
Laboratory experts: The recombinant protein products on the market are basically in the form of lyophilized powder. Only a small amount of the finished product is liquid, and the lyophilized powder is easier to transport and store.
Experimental rookies: How to determine the concentration of added cytokines during the experiment?
Laboratory experts: Since each manufacturer has different production processes or live measurement methods, the activity of cytokines is also different, so the recommended concentration of cytokines can refer to relevant literature or do concentration gradient experiments to determine the best concentration for your own experiments .
Experimental rookies: The molecular weight shown on the gel charts on many cytokine websites is very different from the theoretical molecular weight. What is the reason?
Laboratory experts: First of all, we need to understand two concepts: theoretical molecular weight and apparent molecular weight. The theoretical molecular weight is actually calculated based on the amino acid sequence of the protein; the apparent molecular weight is the protein molecular weight estimated by SDS polyacrylamide gel electrophoresis using a standard reference material of known molecular weight. We all know that the difference between the theoretical molecular weight and the apparent molecular weight is very common in the experiment. The molecular weight of the two on many websites is very different. A large part of it is due to the structure of the protein itself such as protein glycosylation.
Experimental rookies: How to choose the cytokine with good quality?
Laboratory experts: The influence of cytokines on the experiment cannot be underestimated. Once the selection fails, the experiment will not be carried out smoothly, wasting time and effort, so it is very important to choose a cytokine supplier with guaranteed quality. When we choose suppliers, we generally choose companies with good reputation, because companies with good reputation will carry out various quality control on their protein products to ensure the quality of the protein and the experimental effect. It is recommended to read the instructions carefully before purchasing, on the one hand, you can understand the basic information of the protein, on the other hand, the instruction manual will also provide a variety of data such as protein purity, endotoxin content, SDS-PAGE gel map. Of course, biological activity is also a factor to consider when choosing protein products. For example, BaF3 mouse pro-B cells transfected with human CXCR3 were treated with chemokine CCL10 to measure the chemotactic ability of CCL10; TGF-beta 1 was used to inhibit IL-4 induced HT-2 cell proliferation To detect the biological activity of TGF-beta 1.
Product NO Product Name PRP1012 Human IL-6 protein PRP1013 Human TNF-alpha protein PRP1010 Human bFGF protein, His Tag PRP1011 Mouse bFGF protein, His Tag PRP1014 Human IFN-gamma protein, His Tag PRP1015 Mouse IFN-gamma protein, His Tag
Abbkine’s cytokines have high quality guarantee:
Cell-based biological activity assay.
Complete quality control system.
Low endotoxin levels.
High purity,> 95%.
Lyophilized powder form.
Abbkine specializes in the fields of proteinology and cytology, and is committed to innovating and developing various antibodies, proteins, analytical reagents and kits, with a view to becoming a key promoter in the fields of life science research and development, drug research and development. We provide you with the favorite products of protein and immunological research users, from basic immunological products, such as protein extraction and quantification, to the internal reference labeling antibodies, primary antibodies and secondary antibodies of immunological experiments, etc .; the favorite products of cell research users, from Dyes and kits for detecting the state of cells, kits for extracting organelles, staining and tracking of cell substructures and cell metabolism detection products, and cytokine and protein detection kits for cell culture, only to help your research career !
About Abbkine
Our position: Serve global users of cell and protein research, and provide users with economical and technical product solutions through application processes and product portfolios.
Our mission: to stimulate our inner creativity, provide competitive biomedical products and services, and continue to create maximum value for customers.
Our vision: to be a respected, world-class supplier of biomedical products and services.
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IFN-{gamma}-induced chemokines are required for CXCR3-mediated T cell recruitment and anti-tumor efficacy of anti-HER2/CD3 bispecific antibody
Purpose: The response to cancer immune therapy is dependent on endogenous tumor reactive T cells. To bypass this requirement, CD3-bispecific antibodies have been developed to induce a polyclonal T cell response against the tumor. Anti-HER2/CD3 T cell-dependent bispecific (TDB) antibody is highly efficacious in the treatment of HER2 over-expressing tumors in mice. Efficacy and immunological effects of anti-HER2/CD3 TDB were investigated in a mammary tumor model with very few T cells prior treatment. We further describe the mechanism for TDB-induced T cell recruitment to tumors. Experimental Design: Immunological effects and mechanism of CD3-bispecific antibody-induced T cell recruitment into spontaneous HER2 over-expressing mammary tumors was studied using human HER2 transgenic, immune-competent mouse models. Results: Anti-HER2/CD3 TDB treatment induced an inflammatory response in tumors converting them from poorly infiltrated to an inflamed, T cell abundant, phenotype. Multiple mechanisms accounted for the TDB-induced increase in T cells within tumors. TDB treatment induced CD8+ T cell proliferation. T cells were also actively recruited post-TDB treatment by IFN-g-dependent T cell chemokines mediated via CXCR3. This active T cell recruitment by TDB-induced chemokine signaling was the dominant mechanism and necessary for the therapeutic activity of anti-HER2/CD3 TDB. Conclusions: In summary, we demonstrate that the activity of anti-HER2/CD3 TDB was not dependent on high level baseline T cell infiltration. Our results suggest that anti-HER2/CD3 TDB may be efficacious in patients and indications that respond poorly to checkpoint inhibitors. An active T cell recruitment mediated by TDB-induced chemokine signaling was the major mechanism for T cell recruitment.
https://ift.tt/2lHOSJf
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B cell phenotypes, signaling and their roles in secretion of antibodies in systemic lupus erythematosus
Publication date: Available online 5 August 2017
Source:Clinical Immunology
Author(s): Yoshiya Tanaka, Satoshi Kubo, Shigeru Iwata, Maiko Yoshikawa, Shingo Nakayamada
B cells play a pivotal role in the initiation and perpetuation of SLE. Because SLE is molecularly and clinically heterogeneous, efficacious targeted therapy to clinical remission has not yet been established in SLE. We have found i) statistical clustering between Tfh cells and class-switched memory B cells and the upregulated transition from CXCR5+ IgM memory B cells to CXCR3+ class-switched memory B cells in SLE by 8-color flow cytometry, ii) the involvement of Syk, Btk and JAK in the activation and differentiation of B cells in SLE, iii) SLE patients was divided to 3 groups based on immunophenotypic analysis and statistical analysis and patients in the Tfh/class-switched B cell-dominant group were most refractory to conventional therapies although 3 groups had similar clinical features. Thus, novel therapies targeting Tfh-memory B cell interaction are anticipated in certain subpopulation of SLE patients, which leads to the precision medicine in SLE.
from #ENT via xlomafota13 on Inoreader http://ift.tt/2wjhJrs
from OtoRhinoLaryngology - Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hzeLMv
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Hepatocellular carcinoma and CXCR3 chemokines: a narrative review.
Hepatocellular carcinoma and CXCR3 chemokines: a narrative review. Clin Ter. 2017 Jan-Feb;168(1):e37-e41 Authors: Giusy E, Poupak F Abstract Hepatocellular carcinoma (HCC) results from several factors like viral hepatitis infection [hepatitis B, or C (25%)] or occupational exposure. T-helper (Th)1 inflammatory cells, characterized by interferon (IFN)-γ and interleukin (IL)-2 secretion, predominate in the liver during chronic HCV infection, and chemokines attracting these cells are particularly important in disease progression. Among C-X-C chemokines, the non-ELR group [as IFN-γ-induced protein 10 (IP-10), monokine induced by IFN-γ (MIG) and IFN-inducible T-cell-alpha chemoattractant (I-TAC)], attracts Th1-cells interacting with chemokine C-X-C receptor (CXCR3). IP-10 has uniquely been shown to have prognostic utility as a marker of treatment outcome. IFN- γ-induced chemokines, as MIG and IP-10, may promote lymphocyte recruitment to HCC playing important roles in cancer immunology. The production of CXC chemokines by HCC cell lines has been shown. It has been identified immune-gene signature that predicts patient survival including the chemokine gene IP-10. Inflammatory cytokines (tumour necrosis factor-α, IFN-γ) and Toll-like receptor 3 ligands stimulate intratumoral production of these chemokines which drive T and Natural Killer cells tumor infiltration, leading to enhanced cancer cell death. Furthermore selective recruitment of CXCR3(+) B-cells that bridges proinflammatory IL-17 response and protumorigenic macrophage polarization in HCC has been shown, suggesting that blocking CXCR3(+) B-cell migration or function may help defeat HCC. It has been also shown that the overexpression of IP-10, which induced by liver graft injury, may lead to cisplatin resistance via ATF6/Grp78 ER stress signaling pathway in HCC; IP-10 neutralizing antibody could be a potential adjuvant therapy to sensitize HCC-cisplatin treatment. PMID: 28240761 [PubMed - in process] http://dlvr.it/NVYyGs
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Boster Bio Anti-CXCR3 Antibody Picoband™ catalog # PB9079. Tested in IHC, WB applications. This antibody (CXCR3 antibody) reacts with Human, Rat. Supplied as 100μg/vial in Lyophilized form antibody.
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CXCR3 Antibody is a polyclonal antibody that reacts with Human, Rat. A human CXCR3 antibody is produced against a 19-amino-acid peptide near the carboxy terminus. CXCR3's immunogen is found among the last 50 amino acids. CXCR3 is a fully functional receptor involved in the chemotaxis of malignant B lymphocytes and is expressed on malignant B cells from chronic lymphoproliferative diseases, particularly in individuals with CLL. CXCR3 is discovered to be a unique target for therapeutic intervention early in type 1 diabetes in the absence of known causative factors.
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Anti-PD-1-induced high-grade hepatitis associated with corticosteroid-resistant T cells: a case report
Abstract
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control. Mass cytometry allowed comprehensive phenotyping of circulating lymphocytes and revealed that CD4+ T cells were profoundly depleted by ATG, while CD8+ T cells, B cells, NK cells and monocytes were relatively spared. Multiple abnormalities in CD4+ T cell phenotype were stably present in the patient before disease onset. These included a population of CCR4−CCR6− effector/memory CD4+ T cells expressing intermediate levels of the Th1-related chemokine receptor CXCR3 and abnormally high multi-drug resistance type 1 transporter (MDR1) activity as assessed by a rhodamine 123 excretion assay. Expression of MDR1 has been implicated in steroid resistance and may have contributed to the severity and lack of a sustained steroid response in this patient. The number of CD4+ rhodamine 123-excreting cells was reduced > 3.5-fold after steroid and ATG treatment. This case illustrates the need to consider this form of steroid resistance in patients failing treatment with corticosteroids. It also highlights the need for both better identification of patients at risk and the development of treatments that involve more specific immune suppression.
http://ift.tt/2lkucHJ
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TIM-3 Regulates CD103+ Dendritic Cell Function and Response to Chemotherapy in Breast Cancer
Publication date: 8 January 2018
Source:Cancer Cell, Volume 33, Issue 1
Author(s): Álvaro de Mingo Pulido, Alycia Gardner, Shandi Hiebler, Hatem Soliman, Hope S. Rugo, Matthew F. Krummel, Lisa M. Coussens, Brian Ruffell
Intratumoral CD103+ dendritic cells (DCs) are necessary for anti-tumor immunity. Here we evaluated the expression of immune regulators by CD103+ DCs in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. Combined efficacy was CD8+ T cell dependent and associated with increased granzyme B expression; however, TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors. Gene expression analysis identified upregulation of Cxcl9 within intratumoral DCs during combination therapy, and therapeutic efficacy was ablated by CXCR3 blockade, Batf3 deficiency, or Irf8 deficiency.
Graphical abstract
Teaser
de Mingo Pulido et al. show that intratumoral CD103+ dendritic cells (DCs) highly express TIM-3. Anti-TIM-3 antibody promotes CXCL9 expression by these DCs, which enhances the function of CD8+ T cells, thereby improving paclitaxel's therapeutic activity in breast cancer models.
http://ift.tt/2me4ULT
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Anti-PD-1-induced high-grade hepatitis associated with corticosteroid-resistant T cells: a case report
Abstract
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control. Mass cytometry allowed comprehensive phenotyping of circulating lymphocytes and revealed that CD4+ T cells were profoundly depleted by ATG, while CD8+ T cells, B cells, NK cells and monocytes were relatively spared. Multiple abnormalities in CD4+ T cell phenotype were stably present in the patient before disease onset. These included a population of CCR4−CCR6− effector/memory CD4+ T cells expressing intermediate levels of the Th1-related chemokine receptor CXCR3 and abnormally high multi-drug resistance type 1 transporter (MDR1) activity as assessed by a rhodamine 123 excretion assay. Expression of MDR1 has been implicated in steroid resistance and may have contributed to the severity and lack of a sustained steroid response in this patient. The number of CD4+ rhodamine 123-excreting cells was reduced > 3.5-fold after steroid and ATG treatment. This case illustrates the need to consider this form of steroid resistance in patients failing treatment with corticosteroids. It also highlights the need for both better identification of patients at risk and the development of treatments that involve more specific immune suppression.
http://ift.tt/2lkucHJ
0 notes
Text
Anti-PD-1-induced high-grade hepatitis associated with corticosteroid-resistant T cells: a case report
Abstract
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control. Mass cytometry allowed comprehensive phenotyping of circulating lymphocytes and revealed that CD4+ T cells were profoundly depleted by ATG, while CD8+ T cells, B cells, NK cells and monocytes were relatively spared. Multiple abnormalities in CD4+ T cell phenotype were stably present in the patient before disease onset. These included a population of CCR4−CCR6− effector/memory CD4+ T cells expressing intermediate levels of the Th1-related chemokine receptor CXCR3 and abnormally high multi-drug resistance type 1 transporter (MDR1) activity as assessed by a rhodamine 123 excretion assay. Expression of MDR1 has been implicated in steroid resistance and may have contributed to the severity and lack of a sustained steroid response in this patient. The number of CD4+ rhodamine 123-excreting cells was reduced > 3.5-fold after steroid and ATG treatment. This case illustrates the need to consider this form of steroid resistance in patients failing treatment with corticosteroids. It also highlights the need for both better identification of patients at risk and the development of treatments that involve more specific immune suppression.
http://ift.tt/2lkucHJ
0 notes
Text
Anti-PD-1-induced high-grade hepatitis associated with corticosteroid-resistant T cells: a case report
Abstract
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control. Mass cytometry allowed comprehensive phenotyping of circulating lymphocytes and revealed that CD4+ T cells were profoundly depleted by ATG, while CD8+ T cells, B cells, NK cells and monocytes were relatively spared. Multiple abnormalities in CD4+ T cell phenotype were stably present in the patient before disease onset. These included a population of CCR4−CCR6− effector/memory CD4+ T cells expressing intermediate levels of the Th1-related chemokine receptor CXCR3 and abnormally high multi-drug resistance type 1 transporter (MDR1) activity as assessed by a rhodamine 123 excretion assay. Expression of MDR1 has been implicated in steroid resistance and may have contributed to the severity and lack of a sustained steroid response in this patient. The number of CD4+ rhodamine 123-excreting cells was reduced > 3.5-fold after steroid and ATG treatment. This case illustrates the need to consider this form of steroid resistance in patients failing treatment with corticosteroids. It also highlights the need for both better identification of patients at risk and the development of treatments that involve more specific immune suppression.
http://ift.tt/2lkucHJ
0 notes
Text
B cell phenotypes, signaling and their roles in secretion of antibodies in systemic lupus erythematosus
Publication date: Available online 5 August 2017
Source:Clinical Immunology
Author(s): Yoshiya Tanaka, Satoshi Kubo, Shigeru Iwata, Maiko Yoshikawa, Shingo Nakayamada
B cells play a pivotal role in the initiation and perpetuation of SLE. Because SLE is molecularly and clinically heterogeneous, efficacious targeted therapy to clinical remission has not yet been established in SLE. We have found i) statistical clustering between Tfh cells and class-switched memory B cells and the upregulated transition from CXCR5+ IgM memory B cells to CXCR3+ class-switched memory B cells in SLE by 8-color flow cytometry, ii) the involvement of Syk, Btk and JAK in the activation and differentiation of B cells in SLE, iii) SLE patients was divided to 3 groups based on immunophenotypic analysis and statistical analysis and patients in the Tfh/class-switched B cell-dominant group were most refractory to conventional therapies although 3 groups had similar clinical features. Thus, novel therapies targeting Tfh-memory B cell interaction are anticipated in certain subpopulation of SLE patients, which leads to the precision medicine in SLE.
from #ORL-Sfakianakis via xlomafota13 on Inoreader http://ift.tt/2wjhJrs
from OtoRhinoLaryngology - Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hz1Zxn
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HDAC Inhibitor Panobinostat Engages Host Innate Immune Defenses to Promote the Tumoricidal Effects of Trastuzumab in HER2+ Tumors
Histone deacetylase inhibitors (HDACi) may engage host immunity as one basis for their antitumor effects. Herein, we demonstrate an application of this concept using the HDACi panobinostat to augment the antitumor efficacy of trastuzumab (anti-HER2) therapy, through both tumor cell autonomous and nonautonomous mechanisms. In HER2+ tumors that are inherently sensitive to the cytostatic effects of trastuzumab, cotreatment with panobinostat abrogated AKT signaling and triggered tumor regression in mice that lacked innate and/or adaptive immune effector cells. However, the cooperative ability of panobinostat and trastuzumab to harness host anticancer immune defenses was essential for their curative activity in trastuzumab-refractory HER2+ tumors. In trastuzumab-resistant HER2+ AU565pv xenografts and BT474 tumors expressing constitutively active AKT, panobinostat enhanced the antibody-dependent cell-mediated cytotoxicity function of trastuzumab. IFNγ–mediated, CXCR3-dependent increases in tumor-associated NK cells underpinned the combined curative activity of panobinostat and trastuzumab in these tumors. These data highlight the immune-enhancing effects of panobinostat and provide compelling evidence that this HDACi can license trastuzumab to evoke NK-cell–mediated responses capable of eradicating trastuzumab-refractory HER2+ tumors. Cancer Res; 77(10); 2594–606. ©2017 AACR.
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