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https://www.readbyqxmd.com/read/28727142/genomic-and-transcriptomic-heterogeneity-of-colorectal-tumors-arising-in-lynch-syndrome
#1
Hans Binder, Lydia Hopp, Michal R Schweiger, Steve Hoffmann, Frank Jühling, Martin Kerick, Bernd Timmermann, Susann Siebert, Christina Grimm, Lilit Nersisyan, Arsen Arakelyan, Maria Herberg, Peter Buske, Henry Loeffler-Wirth, Maciej Rosolowski, Christoph Engel, Jens Przybilla, Martin Peifer, Nicolaus Friedrichs, Gabriela Moeslein, Margarete Odenthal, Michelle Hussong, Sophia Peters, Stefanie Holzapfel, Jacob Nattermann, Robert Hueneburg, Wolff Schmiegel, Brigitte Royer-Pokora, Stefan Aretz, Michael Kloth, Matthias Kloor, Reinhard Buettner, Jörg Galle, Markus Loeffler
Colorectal cancer (CRC) arising in Lynch Syndrome (LS) comprises tumors with constitutional mutations in DNA mismatch-repair genes. Whole-genome and transcriptome studies of LS-CRC are still missing to address questions about similarities and differences of mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch-repair in LS colonic mucosa and the possible role of immune editing...
July 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28725958/immune-surveillance-plays-a-role-in-locally-aggressive-giant-cell-lesions-of-bone
#2
REVIEW
Ahmad Al-Sukaini, Francis J Hornicek, Zachary S Peacock, Leonard B Kaban, Soldano Ferrone, Joseph H Schwab
BACKGROUND: Giant cell lesions are locally aggressive intraosseous neoplasms with capacity to metastasize. The role of immune surveillance in the pathophysiology of giant cell lesions is poorly understood, and understanding what role the immune system plays in giant cell lesions may lead to the development of more effective treatment. The aim of this study was to explore the role of immune surveillance in giant cell lesions by examining the expression of the HLA class I and class II antigens and tumor infiltrating lymphocytes...
July 19, 2017: Clinical Orthopaedics and related Research
https://www.readbyqxmd.com/read/28724663/pd-l1-expression-and-immune-escape-in-melanoma-resistanceto-mapk-inhibitors
#3
Hojabr Kakavand, Robert V Rawson, Gulietta M Pupo, Jean Y H Yang, Alexander M Menzies, Matteo S Carlino, Richard F Kefford, Julie R Howle, Robyn Saw, John F Thompson, James S Wilmott, Georgina V Long, Richard A Scolyer, Helen Rizos
Purpose: To examine the relationship between immune activity, PD-L1 expression and tumor cell signaling, in metastatic melanomas prior to and during treatment with targeted MAPK inhibitors. <p>Experimental design: Thirty-eight tumors from 17 patients treated with BRAF inhibitor (n=12) or combination BRAF/MEK inhibitors (n=5) with known PD-L1 expression were analyzed. RNA expression arrays were performed on all pre-treatment (PRE, n=17), early during treatment (EDT, n=8) and progression (PROG, n=13) biopsies...
July 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28724442/impact-of-obesity-on-the-response-to-tumor-necrosis-factor-inhibitors-in-axial-spondyloarthritis
#4
Raphael Micheroli, Monika Hebeisen, Lukas M Wildi, Pascale Exer, Giorgio Tamborrini, Jürg Bernhard, Burkhard Möller, Pascal Zufferey, Michael J Nissen, Almut Scherer, Adrian Ciurea
BACKGROUND: Few studies have investigated the impact of obesity on the response to tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). The aim of our study was to investigate the impact of different body mass index (BMI) categories on TNFi response in a large cohort of patients with axSpA. METHODS: Patients with axSpA within the Swiss Clinical Quality Management (SCQM) program were included in the current study if they fulfilled the Assessment in Spondyloarthritis International Society (ASAS) criteria for axSpA, started a first TNFi after recruitment, and had available BMI data as well as a baseline and follow-up visit at 1 year (±6 months)...
July 19, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28713871/immune-dysfunctionality-of-replicative-senescent-mesenchymal-stromal-cells-is-corrected-by-ifn%C3%AE-priming
#5
Raghavan Chinnadurai, Devi Rajan, Spencer Ng, Kenneth McCullough, Dalia Arafat, Edmund K Waller, Larry J Anderson, Greg Gibson, Jacques Galipeau
Industrial-scale expansion of mesenchymal stromal cells (MSCs) is often used in clinical trials, and the effect of replicative senescence on MSC functionality is of mechanistic interest. Senescent MSCs exhibit cell-cycle arrest, cellular hypertrophy, and express the senescent marker β-galactosidase. Although both fit and senescent MSCs display intact lung-homing properties in vivo, senescent MSCs acquire a significant defect in inhibiting T-cell proliferation and cytokine secretion in vitro. IFNγ does not upregulate HLA-DR on senescent MSCs, whereas its silencing did not reverse fit MSCs' immunosuppressive properties...
April 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/28711734/immunohistochemical-investigations-on-the-expression-of-programmed-cell-death-ligand-1-human-leukocyte-antigens-g-and-e-and-granzyme-b-in-intraoral-mucoepidermoid-carcinoma
#6
Carla Mosconi, Diego Antônio Costa Arantes, Andréia Souza Gonçalves, Rita de Cássia Gonçalves Alencar, José Carlos Oliveira, Tarcília Aparecida Silva, Elismauro Francisco Mendonça, Aline Carvalho Batista
OBJECTIVE: To identify the expression of nonclassical human leukocyte antigen G and E (HLA-G and -E), programmed cell death ligand-1 (PD-L1) and granzyme B (GB) in intraoral mucoepidermoid carcinomas (MECs), and to assess whether such expressions are related to metastasis, survival, staging, tumor grade and number of GB-positive cells. DESIGN: For this cross-sectional study, samples of MEC (n=30) were selected and classified as low-grade (LG), intermediate-grade (IG) or high-grade (HG), according to the WHO grading system...
July 8, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28710313/ex-vivo-pd-l1-pd-1-pathway-blockade-reverses-dysfunction-of-circulating-cea-specific-t-cells-in-pancreatic-cancer-patients
#7
Yuan Chen, Shao-An Xue, Goran Hamid Mohammad, Stephen P Pereira, Emma Morris, Shahriar Behboudi
Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer (PC). In this study, we have characterised the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2 restricted peptide, pCEA691-699, isolated from the peripheral T cell repertoire of PC patients and sought to determine if ex vivo PD-L1 & TIM3 blockade could enhance CTL function. CD8(+) T cell lines were generated from peripheral blood mononuclear cells (PBMCs) of 18 HLA-A2(+) patients with PC and from 15 healthy controls...
July 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28701569/distinct-tertiary-lymphoid-structure-associations-and-their-prognostic-relevance-in-her2-positive-and-negative-breast-cancers
#8
Xia Liu, Julia Y S Tsang, Thazin Hlaing, Jintao Hu, Yun-Bi Ni, Siu Ki Chan, Sai Yin Cheung, Gary M Tse
BACKGROUND: The presence of tumor infiltrating lymphocytes (TIL) is associated with favorable prognosis. Recent evidence suggested that not only their density, but also the spatial organization as tertiary lymphoid structures (TLS), play a key role in determining patient survival. MATERIALS AND METHODS: In a cohort of 248 breast cancers, the clinicopathologic association and prognostic role of TLS was examined. RESULTS: Tertiary lymphoid structures were associated with higher tumor grade, apocrine phenotype, necrosis, extensive in situ component, lymphovascular invasion (LVI), and high TIL...
July 12, 2017: Oncologist
https://www.readbyqxmd.com/read/28701512/imatinib-and-nilotinib-off-target-effects-on-human-nk-cells-monocytes-and-m2-macrophages
#9
Francesca Bellora, Alessandra Dondero, Maria Valeria Corrias, Beatrice Casu, Stefano Regis, Fabio Caliendo, Alessandro Moretta, Mario Cazzola, Chiara Elena, Luciana Vinti, Franco Locatelli, Cristina Bottino, Roberta Castriconi
Tyrosine kinase inhibitors (TKIs) are used in the clinical management of hematological neoplasms. Moreover, in solid tumors such as stage 4 neuroblastomas (NB), imatinib showed benefits that might depend on both on-target and immunological off-target effects. We investigated the effects of imatinib and nilotinib on human NK cells, monocytes, and macrophages. High numbers of monocytes died upon exposure to TKI concentrations similar to those achieved in patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunostimulatory cytokines, and degranulated in the presence of NB cells...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28699110/immune-selection-during-tumor-checkpoint-inhibition-therapy-paves-way-for-nk-cell-missing-self-recognition
#10
REVIEW
Karl-Johan Malmberg, Ebba Sohlberg, Jodie P Goodridge, Hans-Gustaf Ljunggren
The ability of NK cells to specifically recognize cells lacking expression of self-MHC class I molecules was discovered over 30 years ago. It provided the foundation for the "missing self" hypothesis. Research in the two past decades has contributed to a detailed understanding of the molecular mechanisms that determine the specificity and strength of NK cell-mediated "missing self" responses to tumor cells. However, in light of the recent remarkable breakthroughs in clinical cancer immunotherapy, the cytolytic potential of NK cells still remains largely untapped in clinical settings...
July 11, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28696685/modeling-sequence-dependent-peptide-fluctuations-in-immunologic-recognition
#11
Cory M Ayres, Timothy P Riley, Steven A Corcelli, Brian M Baker
In cellular immunity, T cells recognize peptide antigens bound and presented by major histocompatibility complex (MHC) proteins. The motions of peptides bound to MHC play a significant role in determining immunogenicity. However, existing approaches for investigating peptide/MHC motional dynamics are challenging or of low throughput, hindering the development of algorithms for predicting immunogenicity from large databases, such as those of tumor or genetically unstable viral genomes. We addressed this by performing exhaustive molecular dynamics simulations on a large structural database of peptides bound to the most commonly expressed human class I MHC protein, HLA-A*0201...
July 11, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28695292/specificity-of-inhibitory-kirs-enables-nk-cells-to-detect-changes-in-an-altered-peptide-environment
#12
Paola Carrillo-Bustamante, Rob J de Boer, Can Keşmir
The activity of natural killer (NK) cells is tightly regulated by inhibitory and activating receptors. Inhibitory killer immunoglobulin-like receptors (iKIRs) survey the surface of target cells by monitoring the expression of human leukocyte antigen (HLA) class I. The binding of iKIRs has been shown to be sensitive to the peptides presented by HLA class I, implying that iKIRs have the ability to detect the changes in the repertoire of peptide-HLA class I complexes (pHLA), a process occurring during viral infection and in tumor cells...
July 10, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28693405/genetics-and-immunodysfunction-underlying-beh%C3%A3-et-s-disease-and-immunomodulant-treatment-approaches
#13
Arash Salmaninejad, Arezoo Gowhari, Seyedmojtaba Hosseini, Saeed Aslani, Meysam Yousefi, Tayyeb Bahrami, Masoume Ebrahimi, Abolfazl Nesaei, Masoud Zal
Behçet's disease (BD) is a chronic autoimmune condition primarily prevalent in populations along the Mediterranean Sea. The exact etiology of BD has not been fully explained yet, but the disease occurrence is associated with a genetic factor, human leukocyte antigen (HLA)-B51 antigen. Among the various immunodysfunctions that are found in BD, patients are increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin (IL)-10...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28693175/functional-analysis-of-cd14-hla-dr-low-myeloid-derived-suppressor-cells-in-patients-with-lung-squamous-cell-carcinoma
#14
Yun Chen, Guichang Pan, Dongbo Tian, Yifei Zhang, Taoping Li
Immunomodulatory therapy is a potential effective treatment for advanced cancer that may provide an alternative to chemotherapy, which patients can experience adverse side effects to. Myeloid-derived suppressor cells (MDSCs) have been demonstrated to cause T-cell tolerance in rodents and humans; however, little is known about the role of MDSCs in squamous cell carcinoma. In the present study, the role of MDSCs in lung squamous cell carcinoma was investigated. Peripheral blood from 78 patients with lung squamous cell carcinoma and 30 healthy controls was examined for the presence and function of human MDSCs, denoted as monocyte differentiation antigen CD14-positive HLA class II histocompatibility antigen DR-negative/low (CD14(+) HLA-DR(-/low)) cells by flow cytometry...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28687085/regulation-of-early-growth-response-2-expression-by-secreted-frizzled-related-protein-1
#15
Kelly J Gregory, Stephanie M Morin, Sallie S Schneider
BACKGROUND: Secreted frizzled-related protein 1 (SFRP1) expression is down-regulated in a multitude of cancers, including breast cancer. Loss of Sfrp1 also exacerbates weight gain as well as inflammation. Additionally, loss of SFRP1 enhances TGF-β signaling and the downstream MAPK pathway. TGF-β has been shown to increase the expression of Early Growth Response 2 (EGR2), a transcription factor implicated in immune function in a wide variety of cell types. The work described here was initiated to determine whether SFRP1 modulation affects TGF-β mediated EGR2 expression in mammary tissues as well as macrophage polarization...
July 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28679396/identification-of-new-muc1-epitopes-using-hla-transgenic-animals-implication-for-immunomonitoring
#16
Tanja Scheikl-Gatard, Caroline Tosch, François Lemonnier, Ronald Rooke
BACKGROUND: The success of immunotherapeutics in oncology and the search for further improvements has prompted revisiting the use of cancer vaccines. In this context, knowledge of the immunogenic epitopes and the monitoring of the immune response cancer vaccines generate are essential. MUC1 has been considered one of the most important tumor associated antigen for decades. METHODS: To identify HLA-restricted MUC1 peptides we used eight human MHC class I transgenic mouse lines, together covering more than 80% of the human population...
July 5, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28677424/expansion-of-cancer-germline-antigen-specific-cytotoxic-t-lymphocytes-for-immunotherapy
#17
Deepa Kolaseri Krishnadas, Yali Wang, Kumaran Sundaram, Fanqi Bai, Kenneth G Lucas
The cancer germline antigens MAGE-A1, MAGE-A3, and NY-ESO-1 can be used to target relapsed or therapy-resistant malignant solid tumors, and previous studies have demonstrated that these antigens can be epigenetically upregulated on the surface of tumor cells following exposure to low-dose demethylating chemotherapy agents, such as decitabine. The extent to which cancer germline antigen cytotoxic T lymphocytes can be reliably expanded from healthy donors has not been well characterized, specifically in terms of whether these T cells consistently kill antigen-bearing targets or simply produce interferon-γ in the presence of the antigen...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28664991/artificial-human-antigen-presenting-cells-are-superior-to-dendritic-cells-at-inducing-cytotoxic-t-cell-responses
#18
Hua Li, Shengwen Shao, Jianshu Cai, Danielle Burner, Lingeng Lu, Qiuqiang Chen, Boris Minev, Wenxue Ma
Peptide recognition through the MHC class I molecule by cytotoxic T lymphocytes (CTLs) leads to the killing of cancer cells. A potential challenge for T-cell immunotherapy is that dendritic cells (DCs) are exposed to the MHC class I-peptide complex for an insufficient amount of time. To improve tumor antigen presentation to T cells and thereby initiate a more effective T cell response, we generated artificial antigen-presenting cells (aAPCs) by incubating human immature DCs (imDCs) with poly(lactic-co-glycolic) acid nanoparticles (PLGA-NPs) encapsulating tumor antigenic peptides, followed by the maturation with lipopolysaccharide (LPS)...
June 30, 2017: Immunology
https://www.readbyqxmd.com/read/28659922/a-poly-lactic-co-glycolic-acid-nanovaccine-based-on-chimeric-peptides-from-different-leishmania-infantum-proteins-induces-dendritic-cells-maturation-and-promotes-peptide-specific-ifn%C3%AE-producing-cd8-t-cells-essential-for-the-protection-against-experimental-visceral
#19
Evita Athanasiou, Maria Agallou, Spyros Tastsoglou, Olga Kammona, Artemis Hatzigeorgiou, Costas Kiparissides, Evdokia Karagouni
Visceral leishmaniasis, caused by Leishmania (L.) donovani and L. infantum protozoan parasites, can provoke overwhelming and protracted epidemics, with high case-fatality rates. An effective vaccine against the disease must rely on the generation of a strong and long-lasting T cell immunity, mediated by CD4(+) TH1 and CD8(+) T cells. Multi-epitope peptide-based vaccine development is manifesting as the new era of vaccination strategies against Leishmania infection. In this study, we designed chimeric peptides containing HLA-restricted epitopes from three immunogenic L...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28659916/hla-bw4-i-80-isoform-differentially-influences-clinical-outcome-as-compared-to-hla-bw4-t-80-and-hla-a-bw4-isoforms-in-rituximab-or-dinutuximab-based-cancer-immunotherapy
#20
Amy K Erbe, Wei Wang, Patrick K Reville, Lakeesha Carmichael, KyungMann Kim, Eneida A Mendonca, Yiqiang Song, Jacquelyn A Hank, Wendy B London, Arlene Naranjo, Fangxin Hong, Michael D Hogarty, John M Maris, Julie R Park, M F Ozkaynak, Jeffrey S Miller, Andrew L Gilman, Brad Kahl, Alice L Yu, Paul M Sondel
Killer-cell immunoglobulin-like receptors (KIRs) are a family of glycoproteins expressed primarily on natural killer cells that can regulate their function. Inhibitory KIRs recognize MHC class I molecules (KIR-ligands) as ligands. We have reported associations of KIRs and KIR-ligands for patients in two monoclonal antibody (mAb)-based trials: (1) A Children's Oncology Group (COG) trial for children with high-risk neuroblastoma randomized to immunotherapy treatment with dinutuximab (anti-GD2 mAb) + GM-CSF + IL-2 + isotretinion or to treatment with isotretinoin alone and (2) An Eastern Cooperative Oncology Group (ECOG) trial for adults with low-tumor burden follicular lymphoma responding to an induction course of rituximab (anti-CD20 mAb) and randomized to treatment with maintenance rituximab or no-maintenance rituximab...
2017: Frontiers in Immunology
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