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Tumor HLA

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https://www.readbyqxmd.com/read/27911124/the-impact-of-interferon-alpha2-on-hla-genes-in-patients-with-polycythemia-vera-and-related-neoplasms
#1
Vibe Skov, Caroline Hasselbalch Riley, Mads Thomassen, Lasse Kjær, Thomas Stauffer Larsen, Ole Weis Bjerrum, Torben A Kruse, Hans Carl Hasselbalch
Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class I and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27909080/ankylosing-spondylitis-versus-nonradiographic-axial-spondyloarthritis-comparison-of-tumor-necrosis-factor-inhibitor-effectiveness-and-effect-of-hla-b27-status-an-observational-cohort-study-from-the-nationwide-danbio-registry
#2
Bente Glintborg, Inge J Sørensen, Mikkel Østergaard, Lene Dreyer, Abdiweli A Mohamoud, Niels S Krogh, Oliver Hendricks, Lis S Andersen, Johnny L Raun, Marcin R Kowalski, Laura Danielsen, Randi Pelck, Henrik Nordin, Jens K Pedersen, Dorte G A Kraus, Susan R Christensen, Inger M J Hansen, Jakob Esbesen, Annette Schlemmer, Anne G Loft, Nabil Al Chaer, Lone Salomonsen, Merete L Hetland
OBJECTIVE: To compare baseline disease activity and treatment effectiveness in biologic-naive patients with nonradiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) who initiate tumor necrosis factor inhibitor (TNFi) treatment and to study the role of potential confounders (e.g., HLA-B27 status). METHODS: Observational cohort study based on prospectively registered data in the nationwide DANBIO registry. We used Kaplan-Meier plots, Cox, and logistic regression analyses to study the effect of diagnosis (nr-axSpA vs AS) and potential confounders (sex/age/start yr/HLA-B27/disease duration/TNFi-type/smoking/baseline disease activity) on TNFi adherence and response [e...
December 1, 2016: Journal of Rheumatology
https://www.readbyqxmd.com/read/27906005/the-role-of-nk-cells-in-hiv-1-protection-autologous-allogeneic-or-both
#3
REVIEW
Jef Hens, Wim Jennes, Luc Kestens
Natural killer (NK) cells specialize in killing virally infected- or tumor cells and are part of the innate immune system. The activational state of NK cells is determined by the balance of incoming activating and inhibitory signals mediated by receptor-ligand binding with the target cell. These receptor-ligand bonds mainly consist of the killer immunoglobulin-like receptors (KIR), which are expressed at the cell surface of NK cells, and their ligands: the highly variable human leukocyte antigen -class I molecules (HLA)...
March 18, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27901642/a-generic-rna-pulsed-dc-based-approach-for-developing-therapeutic-intervention-against-nasopharyngeal-carcinoma
#4
Rajeev K Tyagi, Rajesh Parmar, Naisargee Patel
The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs)...
November 30, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27900264/a-genomic-study-on-distribution-of-human-leukocyte-antigen-hla-a-and-hla-b-alleles-in-lak-population-of-iran
#5
Farhad Shahsavar, Ali-Mohammad Varzi, Seyyed Amir Yasin Ahmadi
Anthropological studies based on the highly polymorphic gene, human leukocyte antigen (HLA), provide useful information for bone marrow donor registry, forensic medicine, disease association studies, as well as infertility treatment, designing peptide vaccines against tumors, and infectious or autoimmune diseases. The aim of this study was to determine HLA-A and HLA-B allele frequencies in 100 unrelated Lak/lᴂk/individuals from Lorestan province of Iran. Finally, we compared the results with that previously described in Iranian population...
March 2017: Genomics Data
https://www.readbyqxmd.com/read/27896368/targeting-of-the-wt191-138-fragment-to-human-dendritic-cells-improves-leukemia-specific-t-cell-responses-providing-an-alternative-approach-to-wt1-based-vaccination
#6
Nergui Dagvadorj, Anne Deuretzbacher, Daniela Weisenberger, Elke Baumeister, Johannes Trebing, Isabell Lang, Carolin Köchel, Markus Kapp, Kerstin Kapp, Andreas Beilhack, Thomas Hünig, Hermann Einsele, Harald Wajant, Götz Ulrich Grigoleit
Due to its immunogenicity and overexpression concomitant with leukemia progression, Wilms tumor protein 1 (WT1) is of particular interest for immunotherapy of AML relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, WT1-specific T-cell responses have mainly been induced by vaccination with peptides presented by certain HLA alleles. However, this approach is still not widely applicable in clinical practice due to common limitations of HLA restriction. Dendritic cell (DC) vaccines electroporated with mRNA encoding full-length protein have also been tested for generating WT1-derived peptides for presentation to T-cells...
November 28, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27895918/classical-and-non-classical-hla-class-i-aberrations-in-primary-cervical-squamous-and-adenocarcinomas-and-paired-lymph-node-metastases
#7
Debbie M Ferns, A Marijne Heeren, Sanne Samuels, Maaike C G Bleeker, Tanja D de Gruijl, Gemma G Kenter, Ekaterina S Jordanova
BACKGROUND: Tumors avoid destruction by cytotoxic T cells (CTL) and natural killer (NK) cells by downregulation of classical human leukocyte antigens (HLA) and overexpression of non-classical HLA. This is the first study to investigate HLA expression in relation to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)), clinicopathological parameters and survival in a large cervical cancer patient cohort. METHODS: Classical (HLA-A and HLA-B/C)- and non-classical HLA molecules (HLA-E and HLA-G) were studied on primary tumors and paired lymph node (LN) metastases from cervical cancer patients (n = 136) by immunohistochemistry...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27894857/cytokine-induced-memory-like-differentiation-enhances-unlicensed-nk-cell-anti-leukemia-and-fc%C3%AE-riiia-triggered-responses
#8
Julia A Wagner, Melissa M Berrien-Elliott, Maximillian Rosario, Jeffrey W Leong, Brea A Jewell, Timothy Schappe, Sara Abdel-Latif, Todd A Fehniger
Cytokine-induced memory-like natural killer (NK) cells differentiate following short-term pre-activation with interleukin (IL)-12, IL-15, and IL-18 and display enhanced effector function in response to cytokines or tumor targets for weeks following the initial pre-activation. Conventional NK cell function is dependent upon a licensing signal, classically delivered by an inhibitory receptor engaging its cognate MHC class I ligand. How licensing status integrates with cytokine-induced memory-like NK cell responses is unknown...
November 25, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27891225/unraveling-the-role-of-preexisting-immunity-in-prostate-cancer-patients-vaccinated-with-a-her-2-neu-hybrid-peptide
#9
Ioannis F Voutsas, Eleftheria A Anastasopoulou, Panagiotis Tzonis, Michael Papamichail, Sonia A Perez, Constantin N Baxevanis
BACKGROUND: Cancer vaccines aim at eliciting not only an immune response against specific tumor antigens, but also at enhancing a preexisting immunity against the tumor. In this context, we recently reported on the levels of preexisting immunity in prostate cancer patients vaccinated with the HER-2 hybrid peptide (AE37), during a phase I clinical trial. The purpose of the current study was to correlate between preexisting immunity to the native HER-2 peptide, AE36, and expression of HLA-A2 and -A24 molecules with the clinical outcome...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27871914/neonatal-levels-of-adiponectin-interleukin-10-and-interleukin-12-are-associated-with-the-risk-of-developing-type-1-diabetes-in-childhood-and-adolescence-a-nationwide-danish-case-control-study
#10
Steffen U Thorsen, Christian B Pipper, Stefanie Eising, Kristin Skogstrand, David M Hougaard, Jannet Svensson, Flemming Pociot
BACKGROUND/AIM: An in-depth understanding of the early phase of type 1 diabetes (T1D) pathogenesis is important for targeting primary prevention. We examined if 14 preselected mediators of immune responses differed in neonates that later developed T1D compared to control neonates. METHODS: The study is a case-control study with a 1:2 matching. The individuals were born between 1981 through 2002. Cases were validated using the National Patient Register and the Danish Childhood Diabetes Register...
November 15, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27868339/fasl-and-the-nkg2d-receptor-are-required-for-the-secretion-of-the-tag7-pgrp-s-hsp70-complex-by-the-cytotoxic-cd8-lymphocytes
#11
Lidia P Sashchenko, Elena A Romanova, Olga K Ivanova, Tatiana N Sharapova, Denis V Yashin
Tag7 (PGRP-S or PGLYRP1), while possessing an antimicrobial activity, also exhibits an antitumor effect when in complex with the major heat shock protein Hsp70. The cytotoxic Tag7-Hsp70 complex is secreted by lymphocytes after interaction with the HLA-negative tumors. Previously, we have shown that IL-2 induces formation of the CD4(+) and CD8(+) cytotoxic subpopulations of human lymphocytes, which kill tumor cells through the FasL-Fas interaction. Here, we show that only the CD8(+) T cells are able to secrete the Tag7-Hsp70 complex...
November 20, 2016: IUBMB Life
https://www.readbyqxmd.com/read/27860539/epitope-specific-antitumor-immunity-suppresses-tumor-spread-in-papillary-thyroid-cancer
#12
Margret Ehlers, Anne Kuebart, Hubertus Hautzel, Juergen Enczmann, Anna-Carinna Reis, Matthias Haase, Stephanie Allelein, Till Dringenberg, Christine Schmid, Matthias Schott
CONTEXT: Papillary thyroid cancer (PTC) is characterized by a lymphocytic infiltration. PTC patients with lymphocytic infiltration may have a better clinical outcome. OBJECTIVE: Characterization of tumor epitope-specific immunity and correlation analyses with the clinical outcome. PATIENTS: 150 PTC patients; 40 Hashimoto's thyroiditis (HT) patients; 21 healthy controls; 27.239 healthy Caucasians (for HLA typing). MAIN OUTCOME MEASURES: HLA class I restricted thyroperoxidase (TPO) and thyroglobulin (Tg) epitope-specific T cells (tetramer analyses), correlation analyses between HLA class II phenotypes, T cell immunity, and the clinical course...
November 18, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27859015/hla-e-allelic-genotype-correlates-with-hla-e-plasma-levels-and-predicts-early-progression-in-chronic-lymphocytic-leukemia
#13
Bettina Wagner, Fabiola da Silva Nardi, Sabine Schramm, Thomas Kraemer, Alexander A Celik, Jan Dürig, Peter A Horn, Ulrich Dührsen, Holger Nückel, Vera Rebmann
BACKGROUND: Human leukocyte antigen-E (HLA-E) is a nonclassical major histocompatibility complex class I molecule that recently came into sharper focus as a putative marker of advanced tumor stages and disease progression. In solid tumors, increased HLA-E expression as well as elevated soluble HLA-E (sHLA-E) plasma levels are associated with a poor prognosis; however, a role for HLA-E in hematologic malignancies remains to be established. METHODS: The authors analyzed HLA-E alleles and sHLA-E levels in a cohort of 110 individuals with chronic lymphocytic leukemia (CLL)...
November 2, 2016: Cancer
https://www.readbyqxmd.com/read/27858943/apobec3a-intratumoral-dna-electroporation-in-mice
#14
A Kostrzak, V Caval, M Escande, E Pliquet, J Thalmensi, T Bestetti, M Julithe, L Fiette, T Huet, S Wain-Hobson, P L Demoyen
Human APOBEC3A (A3A) cytidine deaminase shows pro-apoptotic properties resulting from hypermutation of genomic DNA, induction of double stranded DNA breaks (DSBs) and G1 cell cycle arrest. Given this we evaluated the anti-tumor efficacy of A3A by intratumoral electroporation of an A3A expression plasmid. DNA was repeatedly electroporated into B16OVA, B16Luc tumors of C57BL/6J mice as well as the aggressive fibrosarcoma Sarc2 tumor of HLA-A*0201/DRB1*0101 transgenic mice using non-invasive plate electrodes. Intratumoral electroporation of A3A plasmid DNA resulted in regression of ~50% of small B16OVA melanoma tumors which did not rebound in the following two months without treatment...
November 18, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27856426/cytotoxic-t-cells-in-pd-l1-positive-malignant-pleural-mesotheliomas-are-counterbalanced-by-distinct-immunosuppressive-factors
#15
Mark M Awad, Robert E Jones, Hongye Liu, Patrick H Lizotte, Elena V Ivanova, Meghana Kulkarni, Grit S Herter-Sprie, Xiaoyun Liao, Abigail A Santos, Mark A Bittinger, Lauren Keogh, Shohei Koyama, Christina Almonte, Jessie M English, Julianne Barlow, William G Richards, David A Barbie, Adam J Bass, Scott J Rodig, F Stephen Hodi, Kai W Wucherpfennig, Pasi A Jänne, Lynette M Sholl, Peter S Hammerman, Kwok-Kin Wong, Raphael Bueno
PD-L1 immunohistochemical staining does not always predict whether a cancer will respond to treatment with PD-1 inhibitors. We sought to characterize immune cell infiltrates and the expression of T-cell inhibitor markers in PD-L1-positive and PD-L1-negative malignant pleural mesothelioma samples. We developed a method for immune cell phenotyping using flow cytometry on solid tumors that have been dissociated into single-cell suspensions and applied this technique to analyze 43 resected malignant pleural mesothelioma specimens...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27853650/therapeutic-cd94-nkg2a-blockade-improves-natural-killer-cell-dysfunction-in-chronic-lymphocytic-leukemia
#16
Emily M McWilliams, Jennifer M Mele, Carolyn Cheney, Elizabeth A Timmerman, Faraz Fiazuddin, Ethan J Strattan, Xiaokui Mo, John C Byrd, Natarajan Muthusamy, Farrukh T Awan
Natural killer (NK)-cell count is predictive of chronic lymphoid leukemia (CLL) disease progression and their dysfunction is well documented, but the etiology of this is currently lacking. CLL cells have been shown to over-express HLA-E, the natural ligand for NKG2A expressed on NK-cells that generates a distinct negative signal relative to direct NK-cell cytotoxicity in other disease models. Utilizing a novel anti-NKG2A monoclonal blocking antibody (mAb), monalizumab, we explored the in vitro preclinical activity of targeting the NKG2A receptor, and the NKG2A/HLA-E interaction as a mechanism of tumor evasion in CLL patients...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27853647/mini-intronic-plasmid-vaccination-elicits-tolerant-lag3-cd8-t-cells-and-inferior-antitumor-responses
#17
Viswa Teja Colluru, Christopher D Zahm, Douglas G McNeel
Increasing transgene expression has been a major focus of attempts to improve DNA vaccine-induced immunity in both preclinical studies and clinical trials. Novel mini-intronic plasmids (MIPs) have been shown to cause elevated and sustained transgene expression in vivo. We sought to test the antitumor activity of a MIP, compared to standard DNA plasmid immunization, using the tumor-specific antigen SSX2 in an HLA-A2-restricted tumor model. We found that MIP vaccination elicited a greater frequency of antigen-specific CD8(+) T cells when compared to conventional plasmid, and protected animals from subsequent tumor challenge...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27837020/density-of-immunogenic-antigens-does-not-explain-the-presence-or-absence-of-the-t-cell-inflamed-tumor-microenvironment-in-melanoma
#18
Stefani Spranger, Jason J Luke, Riyue Bao, Yuanyuan Zha, Kyle M Hernandez, Yan Li, Alexander P Gajewski, Jorge Andrade, Thomas F Gajewski
Melanoma metastases can be categorized by gene expression for the presence of a T-cell-inflamed tumor microenvironment, which correlates with clinical efficacy of immunotherapies. T cells frequently recognize mutational antigens corresponding to nonsynonymous somatic mutations (NSSMs), and in some cases shared differentiation or cancer-testis antigens. Therapies are being pursued to trigger immune infiltration into non-T-cell-inflamed tumors in the hope of rendering them immunotherapy responsive. However, whether those tumors express antigens capable of T-cell recognition has not been explored...
November 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27825115/scib1-a-huigg1-antibody-dna-vaccination-combined-with-pd-1-blockade-induced-efficient-therapy-of-poorly-immunogenic-tumors
#19
Wei Xue, Victoria A Brentville, Peter Symonds, Katherine W Cook, Hideo Yagita, Rachael L Metheringham, Lindy G Durrant
PURPOSE: We have previously shown that supraoptimal signaling of high avidity T cells leads to high expression of PD-1 and inhibition of proliferation. This study was designed to see if this effect could be mitigated by combining a vaccine that stimulates high avidity T cells with PD-1 blockade. EXPERIMENTAL DESIGN: We investigated the anti-tumor effect of a huIgG1 antibody DNA vaccine (SCIB1) and PD-1 blockade. RESULTS: Vaccination of HLA-DR4 transgenic mice with SCIB1 induced high frequency and avidity T cell responses that resulted in survival (40%) of mice with established B16F1-DR4 tumors...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27821814/genetic-susceptibility-of-eight-nonsynonymous-polymorphisms-in-hla-drb1-gene-to-hepatocellular-carcinoma-in-han-chinese
#20
Yanhui Shi, Weiyu Zhai, Bin Wang, Dongmei Zhao, He Jin, Yuefei Wang, Jidong Zhang, Hongjun An, Zhongze Fu, Kun Zhao, Changzhu Lu
: Backgrounds and Objective: Mounting evidence suggests that human leukocyte antigen (HLA) plays a central role in anti-virus and tumor defense. To test whether genetic variation in HLA-DRB1 gene, a key component of HLA system, can predict its predisposition to hepatocellular carcinoma (HCC), we thereby conducted an association study by genotyping 8 nonsynonymous polymorphisms in HLA-DRB1 gene among 257 HCC patients and 264 controls. RESULTS: All polymorphisms respected the Hardy-Weinberg equilibrium...
November 4, 2016: Oncotarget
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