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https://www.readbyqxmd.com/read/29772523/mhc-b-haplotypes-impact-susceptibility-and-resistance-to-rsv-a-infection
#1
Vishwa Mohini Khare, Vishesh Kumar Saxena, Alka Tomar, Karam Pal Singh, Kunwar Bahadur Singh, Amit Kumar Tiwari
We investigated the impact of haplotype of major histocompatibility complex (MHC)-B on the outcome of infection of Synthetic Dam Line (SDL) broiler strain with Rous Sarcoma Virus (RSV). Genomic analysis of MHC-B haplotypes, revealed a total of 12 known standard haplotypes that constituted to twenty-five different genotypes and one new haplotype of 217 bp size, designated BX . The inoculation of RSV-A in SDL chicks resulted in the development of tumors of progressive or regressive phenotypes with varying tumor profile index (TPI)...
June 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/29769311/tumor-associated-calreticulin-variants-functionally-compromise-the-peptide-loading-complex-and-impair-its-recruitment-of-mhc-i
#2
Najla Arshad, Peter Cresswell
Major histocompatibility complex-I-β2 m dimers (MHC-I) bind peptides derived from intracellular proteins, enabling the immune system to distinguish between normal cells and those expressing pathogen-derived or mutant proteins. The peptides bind to MHC-I in the endoplasmic reticulum (ER), and this binding is facilitated by the peptide-loading complex (PLC), which contains calreticulin (CRT). CRT associates with MHC-I via a conserved glycan present on MHC-I and recruits it to the PLC for peptide binding. Somatic frameshift mutations in CRT (CRT-FS) drive the proliferation of a subset of myeloproliferative neoplasms (MPNs), which are chronic blood tumors...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29765374/mica-129-dimorphism-and-soluble-mica-are-associated-with-the-progression-of-multiple-myeloma
#3
Alessandra Zingoni, Elisabetta Vulpis, Francesca Cecere, Maria G Amendola, Daniel Fuerst, Taron Saribekyan, Adnane Achour, Tatyana Sandalova, Ilaria Nardone, Agnese Peri, Alessandra Soriani, Cinzia Fionda, Elena Mariggiò, Maria T Petrucci, Maria R Ricciardi, Joannis Mytilineos, Marco Cippitelli, Cristina Cerboni, Angela Santoni
Natural killer (NK) cells are immune innate effectors playing a pivotal role in the immunosurveillance of multiple myeloma (MM) since they are able to directly recognize and kill MM cells. In this regard, among activating receptors expressed by NK cells, NKG2D represents an important receptor for the recognition of MM cells, being its ligands expressed by tumor cells, and being able to trigger NK cell cytotoxicity. The MHC class I-related molecule A (MICA) is one of the NKG2D ligands; it is encoded by highly polymorphic genes and exists as membrane-bound and soluble isoforms...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29764444/molecular-and-clinical-characterization-of-ptpn2-expression-from-rna-seq-data-of-996-brain-gliomas
#4
Peng-Fei Wang, Hong-Qing Cai, Chuan-Bao Zhang, Yan-Michael Li, Xiang Liu, Jing-Hai Wan, Tao Jiang, Shou-Wei Li, Chang-Xiang Yan
BACKGROUND: Immune checkpoint inhibitors have been shown to promote antitumor immunity and achieve durable tumor remissions. However, certain tumors are refractory to current immunotherapy. These negative results encouraged us to uncover other therapeutic targets and strategies. PTPN2 (protein tyrosine phosphatase, non-receptor type 2) has been newly identified as an immunotherapy target. Loss of PTPN2 sensitizes the tumor to immunotherapy via IFNγ signaling. METHODS: Here, we investigated the relationship between PTPN2 mRNA levels and clinical characteristics in gliomas...
May 15, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29763778/mage-a-antigens-as-targets-for-cancer-immunotherapy
#5
REVIEW
Erik Schooten, Alessia Di Maggio, Paul M P van Bergen En Henegouwen, Marta M Kijanka
Targeted anti-cancer therapies aim at reducing side effects while retaining their anti-cancer efficacy. Immunotherapies e.g. monoclonal antibodies, adoptive T cell therapy and cancer vaccines are used to combat cancer, but the number of available cancer specific targets is limited and new approaches are needed to generate more effective and patient tailored treatments. Unique cancer intracellular epitopes can be presented on the cell surface by MHC class I molecules, which can function as epitopes for targeted therapies...
April 26, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29755461/efficient-uptake-of-recombinant-lipidated-survivin-by-antigen-presenting-cells-initiates-antigen-cross-presentation-and-antitumor-immunity
#6
Chen-Yi Chiang, Yi-Jyun Chen, Chiao-Chieh Wu, Shih-Jen Liu, Chih-Hsiang Leng, Hsin-Wei Chen
Survivin is overexpressed in various types of human cancer, but rarely expressed in terminally differentiated adult tissues. Thus, survivin is a potential target antigen for a cancer vaccine. However, self-tumor-associated antigens are not highly immunogenic. Bacteria-derived lipoproteins can activate antigen-presenting cells through their toll-like receptors to enhance immune responses. In this context, lipidated survivin is an attractive candidate for cancer immunotherapy. In the present study, recombinant lipidated human survivin (LSur) was prepared from an Escherichia coli -based system...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29754714/membrane-potential-distinctly-modulates-mobility-and-signaling-of-il-2-and-15-receptors-in-t-cells
#7
Éva Nagy, Gábor Mocsár, Veronika Sebestyén, Julianna Volkó, Ferenc Papp, Katalin Tóth, Sándor Damjanovich, György Panyi, Thomas A Waldmann, Andrea Bodnár, György Vámosi
The high electric field across the plasma membrane might influence the conformation and behavior of transmembrane proteins that have uneven charge distributions in or near their transmembrane regions. Membrane depolarization of T cells occurs in the tumor microenvironment and in inflamed tissues because of K+ release from necrotic cells and hypoxia affecting the expression of K+ channels. However, little attention has been given to the effect of membrane potential (MP) changes on membrane receptor function...
May 10, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29752315/formation-of-immune-complexes-with-a-tetanus-derived-b-cell-epitope-boosts-human-t-cell-responses-to-covalently-linked-peptides-in-an-ex-vivo-blood-loop-system
#8
Erika A K Fletcher, Wendy van Maren, Robert Cordfunke, Jasper Dinkelaar, Jeroen D C Codee, Gijs van der Marel, Cornelis J M Melief, Ferry Ossendorp, Jan Wouter Drijfhout, Sara M Mangsbo
Enhancing T cell responses against both viral and tumor Ags requires efficient costimulation and directed delivery of peptide Ags into APCs. Long peptide vaccines are considered favorable vaccine moieties from a clinical perspective, as they can harbor more than one immunogenic epitope enabling treatment of a broader target population. In addition, longer peptides are not extracellularly loaded on MHC class I; rather, they require intracellular processing and will thereby be presented to T cells mainly by professional APCs, thereby avoiding the risk of tolerance induction...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29752262/cd4-t-cell-mediated-rejection-of-mhc-class-ii-positive-tumor-cells-is-dependent-on-antigen-secretion-and-indirect-presentation-on-host-apcs
#9
Ole Audun Werner Haabeth, Marte Fauskanger, Melanie Manzke, Katrin U Lundin, Alexandre Corthay, Bjarne Bogen, Anders Aune Tveita
Tumor-specific CD4+ T cells have been shown to mediate efficient anti-tumor immune responses against cancer. Such responses can occur through direct binding to MHC class II (MHC II)-expressing tumor cells or indirectly via activation of professional antigen-presenting cells (APC) that take up and present the tumor antigen. We have previously shown that CD4+ T cells reactive against an epitope within the Ig light chain variable region of a murine B cell lymphoma can reject established tumors. Given the presence of MHC II molecules at the surface of lymphoma cells, we investigated whether MHC II-restricted antigen presentation on tumor cells alone was required for rejection...
May 11, 2018: Cancer Research
https://www.readbyqxmd.com/read/29739853/mycobacterium-tuberculosis-ppe60-antigen-drives-th1-th17-responses-via-toll-like-receptor-2-dependent-maturation-of-dendritic-cells
#10
Haibo Su, Zhen Zhang, Zijian Liu, Baozhou Peng, Cong Kong, Honghai Wang, Zhi Zhang, Ying Xu
Targeting of Mycobacterium tuberculosis (MTB) PE/PPE antigens that induce type 1 helper T cell (Th1) and Th17 responses represents a crucial strategy for the development of tuberculosis (TB) vaccines. However, only few PE/PPE antigens induce these responses. Here, we sought to determine how the cell wall-associated antigen PPE60 (Rv3478) activates dendritic cell (DC) maturation and T-cell differentiation. We observed that PPE60 induces DC maturation by augmenting the protein expression of cluster of differentiation 80 (CD80) and CD86, and major histocompatibility complex (MHC) class I and MHC class II on the cell surface...
May 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29730801/challenges-and-prospects-of-chimeric-antigen-receptor-t-cell-therapy-in-solid-tumors
#11
REVIEW
Vishal Jindal, Ena Arora, Sorab Gupta
Chimeric antigen receptor (CAR) T cell therapy is a novel and innovative immunotherapy. CAR-T cells are genetically engineered T cells, carrying MHC independent specific antigen receptor and co-stimulatory molecule which can activate an immune response to a cancer specific antigen. This therapy showed great results in hematological malignancies but were unable to prove their worth in solid tumors. Likely reasons for their failure are lack of antigens, poor trafficking, and hostile tumor microenvironment. Excessive amount of research is going on to improve the efficacy of CAR T cell therapy in solid tumors...
May 5, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29723118/protective-effects-of-interferon-tau-against-lipopolysaccharide-induced-embryo-implantation-failure-in-pregnant-mice
#12
Kangfeng Jiang, Jing Yang, Yu Chen, Shuai Guo, Gan Zhao, Haichong Wu, Ganzhen Deng
Interferon-tau (IFN-τ), a novel type I interferon, is produced by trophoblast cells in ruminants. Previous studies have confirmed that IFN-τ could induce immunological tolerance in humans and other species. However, there are few reports on whether IFN-τ has a protective effect on embryo implantation failure caused by excessive inflammation at the maternal-fetal interface. In our study, a mouse model of lipopolysaccharide (LPS)-induced implantation failure was successfully established, and we investigated the protective effects of IFN-τ...
May 3, 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29721380/targeted-overexpression-of-prostacyclin-synthase-inhibits-lung-tumor-progression-by-recruiting-cd4-t-lymphocytes-in-tumors-that-express-mhc-class-ii
#13
Howard Y Li, Maria McSharry, Deandra Walker, Amber Johnson, Jeff Kwak, Bonnie Bullock, Alexander Neuwelt, Joanna M Poczobutt, Trisha R Sippel, Robert L Keith, Mary C M Weiser-Evans, Eric Clambey, Raphael A Nemenoff
Lung-specific overexpression of prostacyclin synthase (PGIS) decreases tumor initiation in murine lung cancer models. Prostacyclin analogs prevent lung tumor formation in mice and reverse bronchial dysplasia in former smokers. However, the effect of prostacyclin on lung cancer progression has not been well studied. We investigated the effects of pulmonary PGIS overexpression in an orthotopic immunocompetent mouse model of lung cancer using two murine lung cancer cell lines. Pulmonary PGIS overexpression significantly inhibited CMT167 lung tumor growth, increased CXCL9 expression, and increased CD4+ tumor-infiltrating lymphocytes...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721164/novel-therapeutic-features-of-disulfiram-against-hepatocellular-carcinoma-cells-with-inhibitory-effects-on-a-disintegrin-and-metalloproteinase-10
#14
Kaku Goto, Jun Arai, Anthony Stephanou, Naoya Kato
Our previous genome-wide association study identified the anti-tumor ligand MHC class I polypeptide-related sequence A ( MICA ) as a susceptibility gene for hepatitis C virus-induced hepatocellular carcinoma (HCC). We subsequently proved that pharmacological restoration of membrane-bound MICA in HCC cells boosted natural killer cell-mediated anti-cancer effects, confirming that a MICA sheddase, a disintegrin and metalloproteinase 10 (ADAM10), is a therapeutic target. We here searched for approved drugs with inhibitory effects on ADAM10 in vitro , and the anti-alcoholism agent, disulfiram, was identified...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719685/selective-imaging-of-cathepsin-l-in-breast-cancer-by-fluorescent-activity-based-probes
#15
Marcin Poreba, Wioletta Rut, Matej Vizovisek, Katarzyna Groborz, Paulina Kasperkiewicz, Darren Finlay, Kristiina Vuori, Dusan Turk, Boris Turk, Guy S Salvesen, Marcin Drag
Cysteine cathepsins normally function in the lysosomal degradation system where they are critical for the maintenance of cellular homeostasis and the MHC II immune response, and have been found to have major roles in several diseases and in tumor progression. Selective visualization of individual protease activity within a complex proteome is of major importance to establish their roles in both normal and tumor cells, thereby facilitating our understanding of the regulation of proteolytic networks. A generally accepted means to monitor protease activity is the use of small molecule substrates and activity-based probes...
February 28, 2018: Chemical Science
https://www.readbyqxmd.com/read/29710479/antigen-adjuvant-effects-of-icariin-in-enhancing-tumor-specific-immunity-in-mastocytoma-bearing-dba-2j-mice
#16
Xiaodi Zhang, Zhichen Kang, Qingjie Li, Jin Zhang, Sha Cheng, Hao Chang, Shanshan Wang, Shufang Cao, Tie Li, Jiawei Li, Yishan Wang, Yu Song, Hao Yu
Cancer immunotherapy has attracted much attention in recent years because of the ability of immune system to identify tumor cells and limit their growth. Icariin (ICA) is a natural flavonoid glucoside isolated from Epimedium plants and has shown a variety of pharmacological activities such as anti-inflammatory effects, immunological regulation and anticancer potency. Furthermore, it has immunoadjuvant effects on enhancing Th1-immune response, suggesting that ICA may serve as an adjuvant for cancer immunotherapy...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29706958/one-year-follow-up-of-natural-killer-cell-activity-in-multiple-myeloma-patients-treated-with-adjuvant-lenalidomide-therapy
#17
Laurie Besson, Emily Charrier, Lionel Karlin, Omran Allatif, Antoine Marçais, Paul Rouzaire, Lucie Belmont, Michel Attal, Christine Lombard, Gilles Salles, Thierry Walzer, Sébastien Viel
Multiple myeloma (MM) is a proliferation of tumoral plasma B cells that is still incurable. Natural killer (NK) cells can recognize and kill MM cells in vitro and can limit MM growth in vivo . Previous reports have shown that NK cell function is impaired during MM progression and suggested that treatment with immunomodulatory drugs (IMIDs) such as lenalidomide (LEN) could enhance it. However, the effects of IMIDs on NK cells have been tested mostly in vitro or in preclinical models and supporting evidence of their effect in vivo in patients is lacking...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29703841/a-her2-targeting-antibody-drug-conjugate-trastuzumab-deruxtecan-ds-8201a-enhances-antitumor-immunity-in-a-mouse-model
#18
Tomomi Nakayama Iwata, Chiaki Ishii, Saori Ishida, Yusuke Ogitani, Teiji Wada, Toshinori Agatsuma
Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate with a topoisomerase I inhibitor exatecan derivative (DX-8951 derivative, DXd), has been reported to exert potent antitumor effects in xenograft mouse models and clinical trials. In this study, the immune system-activating ability of DS-8201a was assessed. DS-8201a significantly suppressed tumor growth in an immunocompetent mouse model with human HER2-expressing CT26.WT (CT26.WT-hHER2) cells. Cured immunocompetent mice rejected not only re-challenged CT26...
April 27, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29699516/reduction-of-mhc-i-expression-limits-t-lymphocyte-mediated-killing-of-cancer-initiating-cells
#19
Brian J Morrison, Jason C Steel, John C Morris
BACKGROUND: It has been proposed that cancer establishment, maintenance, and recurrence may be attributed to a unique population of tumor cells termed cancer-initiating cells (CICs) that may include characteristics of putative cancer stem cell-like cells. Studies in lung cancer have shown that such cells can be enriched and propagated in vitro by culturing tumor cells in serum-free suspension as tumorspheres. CICs have been characterized for their phenotype, stem cell-like qualities, and their role in establishing tumor and maintaining tumor growth...
April 26, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29698800/mhc-class-i-presented-antigens-from-malignancies-a-perspective-on-analytical-characterization-immunogenicity
#20
Maike Schmidt, Jennie R Lill
The field of cancer immunotherapy has expanded rapidly in the past few years, with many new approaches entering the clinic for T cell mediated killing of tumors. Several of these clinical approaches involve the exploitation of a CD8 + T cell response against MHC I presented tumor antigens. Here, we describe the types of tumor antigens which are considered as targets in the design of T cell based therapeutic approaches, the rationale for targeting MHC I antigens and the analytical tools commonly employed for the discovery of MHC I presented peptides...
April 23, 2018: Journal of Proteomics
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