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https://www.readbyqxmd.com/read/29656492/pd-1-blockade-cellular-vesicles-for-cancer-immunotherapy
#1
Xudong Zhang, Chao Wang, Jinqiang Wang, Quanyin Hu, Benjamin Langworthy, Yanqi Ye, Wujin Sun, Jing Lin, Tianfu Wang, Jason Fine, Hao Cheng, Gianpietro Dotti, Peng Huang, Zhen Gu
Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD-L1 that exhausts antigen-specific CD8+ T cells through PD-1 receptors. Checkpoint blockade antibodies against PD-1 or PD-L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting PD-1 receptors on their membranes, which enhance antitumor responses by disrupting the PD-1/PD-L1 immune inhibitory axis, are reported...
April 14, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29656444/predicting-therapeutic-response-to-fingolimod-treatment-in-multiple-sclerosis-patients
#2
Bibiana Quirant-Sánchez, José V Hervás-García, Aina Teniente-Serra, Luis Brieva, Ester Moral-Torres, Antonio Cano, Elvira Munteis, María J Mansilla, Silvia Presas-Rodriguez, Juan Navarro-Barriuso, Cristina Ramo-Tello, Eva M Martínez-Cáceres
AIMS: Fingolimod, an orally active immunomodulatory drug for relapsing-remitting multiple sclerosis (RRMS), sequesters T cells in lymph nodes through functional antagonism of the sphingosine-1-phosphate receptor, reducing the number of potential autoreactive cells that migrate to the central nervous system. However, not all RRMS patients respond to this therapy. Our aim was to test the hypothesis that by immune-monitoring RRMS patient's leukocyte subpopulations it is possible to find biomarkers associated with clinical response to fingolimod...
April 15, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29656112/influence-of-immunosuppressive-drugs-on-the-cd30-molecule-in-kidney-transplanted-patients
#3
Patricia Cristina Grenzi, Érika Fernandes Campos, Hélio Tedesco-Silva, Claudia Rosso Felipe, Maria Fernanda Soares, José Medina-Pestana, Hinrich Peter Hansen, Maria Gerbase-DeLima
BACKGROUND: Soluble CD30 (sCD30) is a suggested marker for kidney transplantation outcomes. We investigated whether sCD30 serum levels are influenced by immunosuppression and whether they correlate with findings in protocol biopsies and with CD30 gene expression in peripheral blood mononuclear cells (PBMC). METHODS: We studied 118 kidney transplant recipients that initially received tacrolimus (TAC) and, at month-3, were converted or not to sirolimus (SRL). RESULTS: sCD30 serum levels gradually declined after transplantation, being the decline more pronounced in the SRL group...
April 12, 2018: Human Immunology
https://www.readbyqxmd.com/read/29655912/argemone-oil-an-edible-oil-adulterant-induces-systemic-immunosuppression-in-balb-c-mice-in-an-oral-28-days-repeated-dose-toxicity-study
#4
Payal Mandal, Prachi Tewari, Sachin Kumar, Sarika Yadav, Anjaneya Ayanur, Rajnish K Chaturvedi, Mukul Das, Anurag Tripathi
Consumption of edible oils contaminated with Argemone oil (AO) leads to a clinical condition called "Epidemic dropsy". Earlier studies have reported that metabolism and oxidative stress primarily contributes to AO toxicity, however, the involvement of immune system has not been assessed so far. Therefore, the present study was undertaken to systematically assess the effect of AO exposure on the function of immune system in Balb/c mice. The repeated exposure of AO for 28 days caused prominent regression of spleen and thymus; severe inflammatory changes in spleen depicted by the loss of distinct follicles, increased megakaryocyte infiltration, and enhanced expression levels of inflammatory markers (iNOS & COX-2)...
April 12, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29653163/epstein-barr-virus-presence-as-a-potential-etiology-of-persistent-bladder-inflammation-in-human-interstitial-cystitis-bladder-pain-syndrome
#5
Jia-Fong Jhang, Yung-Hsiang Hsu, Chih-Wen Peng, Yuan-Hong Jiang, Han-Chen Ho, Hann-Chorng Kuo
PURPOSE: Interstitial cystitis/bladder pain syndrome is characterized by bladder inflammation without a bacterial infection. Although viral infection is a potential etiologic cause, few studies are reported. MATERIAL AND METHODS: Bladder specimens were obtained from patients with interstitial cystitis/bladder pain syndrome and patients with stress urinary incontinence (control). Bladder specimens were tested for Epstein-Barr-encoded RNAs by in situ hybridization, Epstein-Barr DNA by quantitative real-time polymerase chain reaction (qPCR), serology, and immunohistochemical staining...
April 10, 2018: Journal of Urology
https://www.readbyqxmd.com/read/29652619/circulating-cytokine-chemokine-concentrations-respond-to-ionizing-radiation-doses-but-not-radiation-dose-rates-granulocyte-colony-stimulating-factor-and-interleukin-18
#6
Juliann G Kiang, Joan T Smith, Sara R Hegge, Natalia I Ossetrova
Exposure to ionizing radiation is a crucial life-threatening factor in nuclear and radiological incidents. It is known that ionizing radiation affects cytokine/chemokine concentrations in the blood of B6D2F1 mice. It is not clear whether radiation dose rates would vary the physiological response. Therefore, in this study we utilized data from two experiments using B6D2F1 female mice exposed to six different dose rates ranging from low to high rates. In one experiment, mice received a total dose of 8 Gy (LD0/30 ) of 60 Co gamma radiation at four dose rates: 0...
April 13, 2018: Radiation Research
https://www.readbyqxmd.com/read/29651892/the-intracerebral-hemorrhage-blood-transcriptome-in-humans-differs-from-the-ischemic-stroke-and-vascular-risk-factor-control-blood-transcriptomes
#7
Boryana Stamova, Bradley P Ander, Glen Jickling, Farah Hamade, Marc Durocher, Xinhua Zhan, Da Zhi Liu, Xiyuan Cheng, Heather Hull, Alan Yee, Kwan Ng, Natasha Shroff, Frank R Sharp
Understanding how the blood transcriptome of human intracerebral hemorrhage (ICH) differs from ischemic stroke (IS) and matched controls (CTRL) will improve understanding of immune and coagulation pathways in both disorders. This study examined RNA from 99 human whole-blood samples using GeneChip® HTA 2.0 arrays to assess differentially expressed transcripts of alternatively spliced genes between ICH, IS and CTRL. We used a mixed regression model with FDR-corrected p(Dx) < 0.2 and p < 0.005 and |FC| > 1...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29651698/mitogenic-activity-of-artocarpus-lingnanensis-lectin-and-its-apoptosis-induction-in-jurkat-t-cells
#8
Linjie Zeng, Lu Li, Qiyan Zeng, Yong Deng, Lijun Yin, Liejun Liao
Lectins are a class of carbohydrate-binding proteins or glycoproteins and used in the purification and characterization of glycoproteins according to their specificity to carbohydrates. In the present study, the mitogenic activity of Artocarpus lingnanensis lectin (ALL) and its apoptosis induction in Jurkat T cells were explored. MTT assay revealed strong mitogenic potential of ALL. Meanwhile, the anti-cancer activity of ALL was also explored using the human leukemic Jurkat T cell line. ALL exhibited strong binding affinity (97%) to the cell membrane, which could be effectively inhibited by N-acetyl-D-galactosaminide (NAD)...
April 12, 2018: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29651443/immature-dendritic-cell-therapy-confers-durable-immune-modulation-in-an-antigen-dependent-and-antigen-independent-manner-in-nonobese-diabetic-mice
#9
Jeannette Lo, Chang-Qing Xia, Ruihua Peng, Michael J Clare-Salzler
Dendritic cell (DC) immunotherapy has been effective for prevention of type 1 diabetes (T1D) in NOD mice but fails to protect if initiated after active autoimmunity. As autoreactivity expands inter- and intramolecularly during disease progression, we investigated whether DCs unpulsed or pulsed with β cell antigenic dominant determinants (DD), subdominant determinants (SD), and ignored determinants (ID) could prevent T1D in mice with advanced insulitis. We found that diabetes was significantly delayed by DC therapy...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29650988/the-c-terminal-hret-sequence-of-kv1-3-regulates-gating-rather-than-targeting-of-kv1-3-to-the-plasma-membrane
#10
Orsolya Voros, Orsolya Szilagyi, András Balajthy, Sándor Somodi, Gyorgy Panyi, Péter Hajdu
Kv1.3 channels are expressed in several cell types including immune cells, such as T lymphocytes. The targeting of Kv1.3 to the plasma membrane is essential for T cell clonal expansion and assumed to be guided by the C-terminus of the channel. Using two point mutants of Kv1.3 with remarkably different features compared to the wild-type Kv1.3 (A413V and H399K having fast inactivation kinetics and tetraethylammonium-insensitivity, respectively) we showed that both Kv1.3 channel variants target to the membrane when the C-terminus was truncated right after the conserved HRET sequence and produce currents identical to those with a full-length C-terminus...
April 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29650750/braf-and-mek-inhibitors-increase-pd1-positive-melanoma-cells-leading-to-a-potential-lymphocyte-independent-synergism-with-anti-pd1-antibody
#11
Martina Sanlorenzo, Igor Vujic, Arianna Floris, Mauro Novelli, Loretta Gammaitoni, Lidia Giraudo, Marco Macagno, Valeria Leuci, Ramona Rotolo, Chiara Donini, Marco Basiricò, Pietro Quaglino, Maria Teresa Fierro, Silvia Giordano, Maria Sibilia, Fabrizio Carnevale-Schianca, Massimo Aglietta, Dario Sangiolo
PURPOSE: BRAF and MEK inhibitors (BRAF/MEKi) favor melanoma-infiltrating lymphocytes, providing the rationale for current combinatorial trials with anti-PD1 antibody. A portion of melanoma cells may express PD1, and anti-PD1 antibody could have a direct anti-tumor effect. Here, we explore if BRAF/MEKi modulate rates of PD1+ melanoma cells, supporting an additional - lymphocyte-independent - basis for their therapeutic combination with anti-PD1 antibody. EXPERIMENTAL DESIGN: With data mining and flow cytometry, we assessed PD1, PDL1/2 expression on melanoma cell lines (CCLE, N=61; validation cell lines, N=7) and melanoma tumors (TCGA, N=214)...
April 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29650518/secretory-igm-exacerbates-tumor-progression-by-inducing-accumulations-of-mdscs-in-mice
#12
Chih-Hang Anthony Tang, Shiun Chang, Ayumi Hashimoto, Yi-Ju Chen, Chang Won Kang, Anthony R Mato, Juan R Del Valle, Dmitry Gabrilovich, Chih-Chi Andrew Hu
Chronic lymphocytic leukemia cells can secrete immunoglobulin M. However, it is not clear whether secretory IgM (sIgM) plays a role in disease progression. We crossed the Eμ-TCL1 mouse model of CLL, in which the expression of human TCL1 oncogene was driven by the V(H) promoter-Ig(H)-Eμ enhancer, with MD4 mice whose B cells produced B cell receptor (membrane-bound IgM) and sIgM with specificity for hen egg lysozyme (HEL). CLL cells developed in these MD4/Eμ-TCL1 mice reactivated a parental Ig gene allele and secreted IgM, and did not recognize HEL...
April 12, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29650230/production-of-spliced-peptides-by-the-proteasome
#13
Nathalie Vigneron, Vincent Stroobant, Violette Ferrari, Joanna Abi Habib, Benoit J Van den Eynde
CD8+ cytolytic T lymphocytes are essential players of anti-tumor immune responses. On tumors, they recognize peptides of about 8-to-10 amino acids that generally result from the degradation of cellular proteins by the proteasome. Until a decade ago, these peptides were thought to solely correspond to linear fragments of proteins that were liberated after the hydrolysis of the peptide bonds located at their extremities. However, several examples of peptides containing two fragments originally distant in the protein sequence challenged this concept and demonstrated that proteasome could also splice peptides together by creating a new peptide bond between two distant fragments...
April 9, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29649688/recombinant-outer-membrane-protein-25c-from-brucella-abortus-induces-th1-and-th2-mediated-protection-against-brucella-abortus-infection-in-mouse-model
#14
Soumya Paul, Bhavani V Peddayelachagiri, Sowmya Nagaraj, Joseph J Kingston, Harsh V Batra
Development of a safe and efficacious vaccine for brucellosis is a long standing challenge for scientists. Recognizing potential antigens towards developing vaccine candidate is crucial. Omp25c, a porin protein of Brucella, is a paralog of two previously identified promising vaccine candidates namely, Omp25 and Omp31, with notable sequence identity. Also, Omp25c is conserved in all major Brucella species. This highlights the possibility of employing this protein in multivalent subunit vaccine based approach of Brucella management...
April 9, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29649639/cobalt-ii-ions-and-nanoparticles-induce-macrophage-retention-by-ros-mediated-down-regulation-of-rhoa-expression
#15
Jing Xu, Junyao Yang, Agata Nyga, Mazdak Ehteramyan, Ana Moraga, Yuanhao Wu, Lingfang Zeng, Martin M Knight, Julia C Shelton
Histological assessments of synovial tissues from patients with failed CoCr alloy hip prostheses demonstrate extensive infiltration and accumulation of macrophages, often loaded with large quantities of particulate debris. The resulting adverse reaction to metal debris (ARMD) frequently leads to early joint revision. Inflammatory response starts with the recruitment of immune cells and requires the egress of macrophages from the inflamed site for resolution of the reaction. Metal ions (Co2+ and Cr3+ ) have been shown to stimulate the migration of T lymphocytes but their effects on macrophages motility are still poorly understood...
April 9, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29649617/reversal-of-t-cell-exhaustion-by-the-first-donor-lymphocyte-infusion-is-associated-with-the-persistently-effective-anti-leukemic-responses-in-patients-with-relapsed-aml-after-allo-hsct
#16
Long Liu, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Kai-Yan Liu, Xiao-Jun Huang
Donor lymphocyte infusion is an effective approach to treat acute myeloid leukemia (AML) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) that significantly improves the survival of relapsed patients. However, the mechanism of an effective anti-leukemic response following DLI in AML relapse remains elusive. Here, we investigated the role of T cell exhaustion in AML relapse after allo-HSCT in prospective cohorts of 41 patients with the first AML relapse and 41 non-relapsed AML controls after allo-HSCT and determined whether DLI exerts effective anti-leukemic effects by reversing T cell exhaustion in the relapsed cohorts by detecting the phenotypes and functions of T cells using flow cytometry...
April 9, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29649548/spontaneous-atopic-dermatitis-due-to-immune-dysregulation-in-mice-lacking-adamts2-and-14
#17
L Dupont, G Ehx, M Chantry, C Monseur, C Leduc, L Janssen, D Cataldo, M Thiry, C Jerome, J-M Thomassin, B Nusgens, J Dubail, F Baron, A Colige
Since its first description, ADAMTS14 has been considered as an aminoprocollagen peptidase based on its high similarity with ADAMTS3 and ADAMTS2. As its importance for procollagen processing was never experimentally demonstrated in vivo, we generated Adamts14-deficient mice. They are healthy, fertile and display normal aminoprocollagen processing. They were further crossed with Adamts2-deficient mice to evaluate potential functional redundancies between these two highly related enzymes. Initial characterizations made on young Adamts2-Adamts14-deficient animals showed the same phenotype as that of Adamts2-deficient mice, with no further reduction of procollagen processing and no significant aggravation of the structural alterations of collagen fibrils...
April 9, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29649215/mobile-phone-specific-electromagnetic-fields-induce-transient-dna-damage-and-nucleotide-excision-repair-in-serum-deprived-human-glioblastoma-cells
#18
Halh Al-Serori, Franziska Ferk, Michael Kundi, Andrea Bileck, Christopher Gerner, Miroslav Mišík, Armen Nersesyan, Monika Waldherr, Manuel Murbach, Tamara T Lah, Christel Herold-Mende, Andrew R Collins, Siegfried Knasmüller
Some epidemiological studies indicate that the use of mobile phones causes cancer in humans (in particular glioblastomas). It is known that DNA damage plays a key role in malignant transformation; therefore, we investigated the impact of the UMTS signal which is widely used in mobile telecommunications, on DNA stability in ten different human cell lines (six brain derived cell lines, lymphocytes, fibroblasts, liver and buccal tissue derived cells) under conditions relevant for users (SAR 0.25 to 1.00 W/kg)...
2018: PloS One
https://www.readbyqxmd.com/read/29648517/preliminary-evidence-of-reductive-stress-in-human-cytotoxic-t-cells-following-exercise
#19
Alex James Wadley, Adrian Holliday, Rhys G Morgan, Kate J Heesom, Sarah Aldred, Derek M Peters, Allain A Bueno, Steven J Coles
This study investigated immunophenotypic differences in intracellular thiol redox state of peripheral blood mononuclear cells (PBMCs) isolated from trained (TR, n=9, mean {plus minus} SD: age 28 {plus minus} 5 years; BMI 23.2 {plus minus} 2.6 kg·m2 ; VO2max 56.9 {plus minus} 6.1 ml·kg-1 ·min-1 ) and recreationally active (RA, n=11, mean {plus minus} SD: age 27 {plus minus} 6 years; BMI 24.2 {plus minus} 3.7 kg·m2 ; VO2max 45.1 {plus minus} 6.4 ml·kg-1 ·min-1 ) participants before and after a maximal aerobic exercise tolerance test...
April 12, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29644257/intravenous-labeling-and-analysis-of-the-content-of-thymic-perivascular-spaces
#20
Roland Ruscher, Kristin A Hogquist
Following development in the thymus, T cells are thought to exit into the periphery predominantly through perivascular spaces (PVS). This exit route is used by conventional T cells, and likely also applies to unconventional T cell subsets, such as precursors of CD8αα and TCRγδ intraepithelial lymphocytes, regulatory T cells and natural killer T cells. Additional cell types might also be found in the PVS and initiate interactions with exiting T cells. The exact content of the PVS, and the processes within, are not well studied...
March 5, 2018: Bio-protocol
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