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https://www.readbyqxmd.com/read/28637877/ex-vivoexpanded-adaptive-nk-cells-effectively-kill-primary-acute-lymphoblastic-leukemia-cells
#1
Lisa L Liu, Vivien Beziat, Vincent Oei Yi Sheng, Aline Pfefferle, Marie Schaffer, Soren Lehmann, Eva Hellstrom-Lindberg, Stefan Soderhall, Mats Heyman, Dan Grander, Karl-Johan Malmberg
Manipulation of human NK cell repertoires promises more effective strategies for NK cell-based cancer immunotherapy. A subset of highly differentiated NK cells, termed adaptive NK cells, expands naturally in vivo in response to human cytomegalovirus (HCMV) infection, carries unique repertoires of inhibitory killer cell immunoglobulin-like receptors (KIRs), and displays strong cytotoxicity against tumor cells. Here, we established a robust and scalable protocol for ex vivo generation and expansion of adaptive NK cells for cell therapy against pediatric acute lymphoblastic leukemia (ALL)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28634589/hla-class-ia-and-ib-polyreactive-anti-hla-e-igg2a-monoclonal-antibodies-tfl-006-and-tfl-007-suppress-anti-hla-igg-production-by-cd19-b-cells-and-proliferation-of-cd4-t-cells-while-upregulating-tregs
#2
REVIEW
Mepur H Ravindranath
The anti-HLA-E IgG2a mAbs, TFL-006 and TFL-007, reacted with all HLA-I antigens, similar to the therapeutic preparations of IVIg. Indeed, IVIg lost its HLA reactivity, when its HLA-E reactivity was adsorbed out. US-FDA approved IVIg to reduce antibodies in autoimmune diseases. But the mechanism underlying IVIg-mediated antibody reduction could not be ascertained due to the presence of other polyclonal antibodies. In spite of it, the cost prohibitive high or low IVIg is administered to patients waiting for donor organ and for allograft recipients for lowering antiallograft antibodies...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28623356/high-risk-human-papillomavirus-e7-alters-host-dna-methylome-and-represses-hla-e-expression-in-human-keratinocytes
#3
Louis Cicchini, Rachel Z Blumhagen, Joseph A Westrich, Mallory E Myers, Cody J Warren, Charlotte Siska, David Raben, Katerina J Kechris, Dohun Pyeon
Human papillomavirus (HPV) infection distinctly alters methylation patterns in HPV-associated cancer. We have recently reported that HPV E7-dependent promoter hypermethylation leads to downregulation of the chemokine CXCL14 and suppression of antitumor immune responses. To investigate the extent of gene expression dysregulated by HPV E7-induced DNA methylation, we analyzed parallel global gene expression and DNA methylation using normal immortalized keratinocyte lines, NIKS, NIKS-16, NIKS-18, and NIKS-16∆E7...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28576831/shifting-the-balance-of-activating-and-inhibitory-natural-killer-receptor-ligands-on-braf-v600e-melanoma-lines-with-vemurafenib
#4
Alexandra Frazao, Marina Colombo, Emmanuelle Fourmentraux-Neves, Meriem Messaoudene, Sylvie Rusakiewicz, Laurence Zitvogel, Eric Vivier, Frederic Vely, Florence Faure, Brigitte Dreno, Houssem Benlalam, Fanny Bouquet, Ariel Savina, Eric Pasmant, Antoine Toubert, Marie Francoise Avril, Anne Caignard
Over 60% of human melanoma tumors bear a mutation in the BRAF gene. The most frequent mutation is a substitution at codon 600 (V600E), leading to a constitutively active BRAF and overactivation of the mitogen-activated protein kinase (MAPK) pathway. Patients harboring mutated BRAF respond to kinase inhibitors such as vemurafenib. However, these responses are transient and relapses are frequent. Melanoma cells are efficiently lysed by activated natural killer (NK) cells. Melanoma cells express several stress-induced ligands that are recognized by activating NK cell receptors...
June 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28566275/fibroblast-adapted-human-cmv-vaccines-elicit-predominantly-conventional-cd8-t-cell-responses-in-humans
#5
Susan E Murray, Pavlo A Nesterenko, Adam L Vanarsdall, Michael W Munks, Savannah M Smart, Eren M Veziroglu, Lavinia C Sagario, Ronzo Lee, Frans H J Claas, Ilias I N Doxiadis, Michael A McVoy, Stuart P Adler, Ann B Hill
Cytomegalovirus (CMV)-based vaccines have shown remarkable efficacy in the rhesus macaque model of acquired immune deficiency syndrome, enabling 50% of vaccinated monkeys to clear a subsequent virulent simian immunodeficiency virus challenge. The protective vaccine elicited unconventional CD8 T cell responses that were entirely restricted by MHC II or the nonclassical MHC I molecule, MHC-E. These unconventional responses were only elicited by a fibroblast-adapted rhesus CMV vector with limited tissue tropism; a repaired vector with normal tropism elicited conventional responses...
May 31, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28521443/loss-of-fas-expression-and-high-expression-of-hla-e-promoting-the-immune-escape-of-early-colorectal-cancer-cells
#6
Renxiang Huang, Dongyang Zhang, Feng Li, Zili Xiao, Meiling Wu, Dongyun Shi, Ping Xiang, Zhijun Bao
Previous studies have investigated the mechanisms of immune evasion of tumor cells in numerous types of advanced solid malignant tumor, and several types of immune preparations have been administered as antitumor adjuvant therapies. However, in the majority of studies, the efficacy of therapies has been revealed to be limited. The present study aimed to investigate the immune evasion mechanisms employed by early colorectal cancer cells and the expression of the molecules associated with immune evasion during the malignant transformation process of normal colorectal epithelial cells to measure the effects of immune intervention for early colorectal cancer, and to improve the efficacy of immunotherapy...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28504668/hla-e-expressing-pluripotent-stem-cells-escape-allogeneic-responses-and-lysis-by-nk-cells
#7
Germán G Gornalusse, Roli K Hirata, Sarah E Funk, Laura Riolobos, Vanda S Lopes, Gabriel Manske, Donna Prunkard, Aric G Colunga, Laïla-Aïcha Hanafi, Dennis O Clegg, Cameron Turtle, David W Russell
Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this 'missing-self' response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C...
May 15, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28475642/mhc-ib-molecule-qa-1-presents-mycobacterium-tuberculosis-peptide-antigens-to-cd8-t-cells-and-contributes-to-protection-against-infection
#8
Yao Bian, Shaobin Shang, Sarah Siddiqui, Jie Zhao, Simone A Joosten, Tom H M Ottenhoff, Harvey Cantor, Chyung-Ru Wang
A number of nonclassical MHC Ib molecules recognizing distinct microbial antigens have been implicated in the immune response to Mycobacterium tuberculosis (Mtb). HLA-E has been identified to present numerous Mtb peptides to CD8+ T cells, with multiple HLA-E-restricted cytotoxic T lymphocyte (CTL) and regulatory T cell lines isolated from patients with active and latent tuberculosis (TB). In other disease models, HLA-E and its mouse homolog Qa-1 can act as antigen presenting molecules as well as regulators of the immune response...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28425192/soluble-hla-e-a-follow-up-biomarker-in-takayasu-arteritis-independent-of-hla-e-genotype
#9
Ruchika Goel, Jayakanthan Kabeerdoss, Hindhumathi Mohan, Sumita Danda, Visali Jayaseelan, T Sathish Kumar, John Jude, Paul Bacon, George Joseph, Debashish Danda
AIM: Disease activity assessment in Takayasu arteritis (TA) is challenging. Human leukocyte antigen E (HLA-E) is shed from endothelium into serum as a soluble molecule (sHLA-E) in response to inflammation. We aimed to study: (i) utility of sHLA-E as a biomarker of disease activity; and (ii) association of HLA-E polymorphism rs1264457 with clinical disease in Asian-Indian TA patients. MATERIALS AND METHODS: In phase-1, sHLA-E levels were estimated in sera of 50 consecutive TA patients at baseline visit and 27 healthy controls...
April 19, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28340094/nlrp2-is-a-suppressor-of-nf-%C3%A6-b-signaling-and-hla-c-expression-in-human-trophoblasts%C3%A2-%C3%A2
#10
Tamara Tilburgs, Torsten B Meissner, Leonardo M R Ferreira, Arend Mulder, Kiran Musunuru, Junqiang Ye, Jack L Strominger
During pregnancy, fetal extravillous trophoblasts (EVT) play a key role in the regulation of maternal T cell and NK cell responses. EVT display a unique combination of human leukocyte antigens (HLA); EVT do not express HLA-A and HLA-B, but do express HLA-C, HLA-E, and HLA-G. The mechanisms establishing this unique HLA expression pattern have not been fully elucidated. The major histocompatibility complex (MHC) class I and class II transcriptional activators NLRC5 and CIITA are expressed neither by EVT nor by the EVT model cell line JEG3, which has an MHC expression pattern identical to that of EVT...
April 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28337381/hla-e-inhibitor-enhances-the-killing-of-neuroblastoma-stem-cells-by-co-cultured-dendritic-cells-and-cytokine-induced-killer-cells-loaded-with-membrane-based-microparticles
#11
Zijun Zhen, Kaibin Yang, Litong Ye, Zhiyao You, Rirong Chen, Ying Liu, Youjian He
Neuroblastoma stem cells (NSCs) can cause drug resistance and tumor recurrence. This study aimed to enhance the lytic effect of dendritic cells (DCs) co-cultured with cytokine-induced killer (CIK) cells. NSCs were obtained by suspension culture, and DC-CIK cells were loaded with extracted NSC membrane-based microparticles (MMPs) before evaluating the lytic effect of DC-CIK cells on NSCs. After inhibiting the function or expression of human leukocyte antigen-E (HLA-E) in NSCs by anti-HLA-E monoclonal antibody or siRNA, the DC-CIK cell lytic effect on NSCs was re-assessed...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28299193/recent-advances-in-major-histocompatibility-complex-mhc-class-i-antigen-presentation-plastic-mhc-molecules-and-tapbpr-mediated-quality-control
#12
REVIEW
Andy van Hateren, Alistair Bailey, Tim Elliott
We have known since the late 1980s that the function of classical major histocompatibility complex (MHC) class I molecules is to bind peptides and display them at the cell surface to cytotoxic T cells. Recognition by these sentinels of the immune system can lead to the destruction of the presenting cell, thus protecting the host from pathogens and cancer. Classical MHC class I molecules (MHC I hereafter) are co-dominantly expressed, polygenic, and exceptionally polymorphic and have significant sequence diversity...
2017: F1000Research
https://www.readbyqxmd.com/read/28258595/transgenic-expression-of-human-leukocyte-antigen-e-attenuates-galko-hcd46-porcine-lung-xenograft-injury
#13
Christopher T Laird, Lars Burdorf, Beth M French, Natalia Kubicki, Xiangfei Cheng, Gheorghe Braileanu, Wenji Sun, Natalie A O'Neill, Arielle Cimeno, Dawn Parsell, Edward So, Andrea Bähr, Nikolai Klymiuk, Carol J Phelps, David Ayares, Agnes M Azimzadeh, Richard N Pierson
BACKGROUND: Lung xenografts remain susceptible to loss of vascular barrier function within hours in spite of significant incremental advances based on genetic engineering to remove the Gal 1,3-αGal antigen (GalTKO) and express human membrane cofactor protein (hCD46). Natural killer cells rapidly disappear from the blood during perfusion of GalTKO.hCD46 porcine lungs with human blood and presumably are sequestered within the lung vasculature. Here we asked whether porcine expression of the human NK cell inhibitory ligand HLA-E and β2 microglobulin inhibits GalTKO...
March 3, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28244222/a-novel-hla-e-allele-hla-e-01-01-01-07-identified-in-a-chinese-leukemia-patient
#14
S-X Wang, Y-P Xu, Li-M He
A novel HLA-E allele, HLA-E*01:01:01:07, was identified in a Chinese leukemia patient.
May 2017: HLA
https://www.readbyqxmd.com/read/28205421/a-novel-hla-e-allele-hla-e-01-01-01-06-identified-in-a-chinese-leukemia-patient
#15
Y-P Xu, S-X Wang, W-X Hong
A novel HLA-E allele, HLA-E*01:01:01:06, was identified in a Chinese leukemia patient.
April 2017: HLA
https://www.readbyqxmd.com/read/28197391/high-nkg2a-expression-contributes-to-nk-cell-exhaustion-and-predicts-a-poor-prognosis-of-patients-with-liver-cancer
#16
Cheng Sun, Jing Xu, Qiang Huang, Mei Huang, Hao Wen, Chuanshan Zhang, Jinyu Wang, Jiaxi Song, Meijuan Zheng, Haoyu Sun, Haiming Wei, Weihua Xiao, Rui Sun, Zhigang Tian
Background and Aims: As the predominant lymphocyte subset in the liver, natural killer (NK) cells have been shown to be highly associated with the outcomes of patients with chronic hepatitis B virus infection (CHB) and hepatocellular carcinoma (HCC). Previously, we reported that NKG2A, a checkpoint candidate, mediates human and murine NK cell dysfunction in CHB. However, NK cell exhaustion and, particularly, the level of NKG2A expression within liver tumors have not been reported. Methods: In this study, we analyzed NKG2A expression and the related dysfunction of NK cells located in intra- or peritumor regions of liver tissue samples from 207 HCC patients, in addition to analyzing disease outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28185362/definitive-class-i-human-leukocyte-antigen-expression-in-gestational-placentation-hla-f-hla-e-hla-c-and-hla-g-in-extravillous-trophoblast-invasion-on-placentation-pregnancy-and-parturition
#17
Rinat Hackmon, Lakmini Pinnaduwage, Jianhong Zhang, Stephen J Lye, Daniel E Geraghty, Caroline E Dunk
PROBLEM: The extravillous trophoblasts (EVT) express HLA-C and HLA-G, but HLA-E and HLA-F are the subject of conflicting reports. In this study, we define the HLA expression profile during active EVT placental implantation, pregnancy development, and parturition. METHOD OF STUDY: Immunohistochemistry, q-PCR, and Western blot were used to investigate HLA-C, HLA-E, and HLA-F placental expression across gestation from the early first trimester, late first trimester, second trimester (n=10 in each), preterm gestation (n=6) to elective term cesarean section and term vaginal deliveries (n=12, 38-41 weeks)...
June 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28159587/evaluation-of-hla-g-hla-e-and-pd-l1-proteins-in-oral-osteosarcomas
#18
Diego Antonio Costa Arantes, Andréia Souza Gonçalves, Bruno Correia Jham, Eliza Carla Barroso Duarte, Élbio Candido de Paula, Henrique Moura de Paula, Elismauro Francisco Mendonça, Aline Carvalho Batista
OBJECTIVE: The aim of this study was to investigate the expression of human leukocyte antigens (HLAs) G and E and programmed death-ligand 1 (PD-L1) in oral osteosarcoma (OO) (n = 13). The relationship between the expression of these molecules and histologic grading and metastasis was also evaluated. STUDY DESIGN: HLA-G, HLA-E, and PD-L1 were identified by immunohistochemistry. Samples of normal bone tissue (n = 6) were used as controls. The sections were evaluated using a semiquantitative scoring system with an immunoreactive score, where a score of 0 was considered absent, ≤2 was low, and >2 was high expression...
December 14, 2016: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28127896/new-insights-in-hla-e-polymorphism-by-refined-analysis-of-the-full-length-gene
#19
T I Olieslagers, C E M Voorter, M Groeneweg, Y Xu, L Wieten, M G J Tilanus
BACKGROUND: Human leukocyte antigen (HLA)-E is a non-classical HLA class I molecule that plays a role in both the innate and the adaptive immune response through interaction with receptors on natural killer- and T-cells. The HLA-E gene is characterized by limited polymorphism compared with the classical HLA loci on chromosome 6. At the start of this study, only 13 variable sites had been identified (IPD-IMGT/HLA Database v3.18.0). While most previous studies focused on polymorphism in exons 2 and 3 or specific gene regions, polymorphism in the other exons and introns could influence protein expression and function as well...
January 27, 2017: HLA
https://www.readbyqxmd.com/read/28012452/expression-of-hla-e-molecules-in-the-placental-tissue-of-women-infected-with-hiv-1-and-uninfected-women
#20
Juliana Martinez, Mariana Rodrigues Santiago, Gustavo Martelli-Palomino, Diego Agra de Souza, Társia Giabardo Alves Silva, Gyl Eanes Barros Silva, Fernando Chahud, Eduardo Antônio Donadi, Ana Paula Morais Fernandes
INTRODUCTION: Expression of HLA-E molecule in the placental extravillous trophoblast is associated with immune system cell inhibition, resulting in immune tolerance to fetus during pregnancy. HIV-1 can infect trophoblast cells and modify the expression of HLA-E, which may inhibit the cytotoxic activity of the immune system. AIM: The aim of this study was to evaluate HLA-E expression in third trimester placental tissue of women infected with HIV-1 and uninfected women...
January 2017: Placenta
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