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https://www.readbyqxmd.com/read/28724788/multiparametric-immune-profiling-in-hpv-oral-squamous-cell-cancer
#1
Zipei Feng, Daniel Bethmann, Matthias Kappler, Carmen Ballesteros-Merino, Alexander Eckert, R Bryan Bell, Allen Cheng, Tuan Bui, Rom Leidner, Walter J Urba, Kent Johnson, Clifford Hoyt, Carlo B Bifulco, Juergen Bukur, Claudia Wickenhauser, Barbara Seliger, Bernard A Fox
Evaluation of T lymphocyte frequency provides prognostic information for patients with oral squamous cell cancer (OSCC). However, the effect of simultaneously evaluating T cell frequency and assessing suppressive elements and defects in antigen-processing machinery (APM) has not been clarified. Simultaneous characterization of CD3+, CD8+, FoxP3+, CD163+, and PD-L1+ cells using multispectral imaging was performed on sections from 119 patients with HPV- OSCC. Expression of β2-microglobulin, MHC class I heavy chain, and large multifunctional peptidase 10 was quantified, and all data were correlated with patient outcome...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28718425/nlrc5-cita-a-key-player-in-cancer-immune-surveillance
#2
REVIEW
Sayuri Yoshihama, Saptha Vijayan, Tabasum Sidiq, Koichi S Kobayashi
Cancer cells need to escape immune surveillance for successful tumor growth. Loss of MHC class I has been described as a major immune evasion strategy in many cancers. MHC class I transactivator (CITA), NLRC5 [nucleotide-binding domain and leucine-rich repeats containing (NLR) family, caspase activation and recruitment domain (CARD) domain containing 5], is a key transcription coactivator of MHC class I genes. Recent genetic studies have revealed that NLRC5 is a major target for cancer immune evasion mechanisms...
January 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28717398/preclinical-evaluation-of-nf-%C3%AE%C2%BAb-triggered-dendritic-cells-expressing-the-viral-oncogenic-driver-of-merkel-cell-carcinoma-for-therapeutic-vaccination
#3
Kerstin F Gerer, Michael Erdmann, Sine R Hadrup, Rikke Lyngaa, Lena-Marie Martin, Reinhard E Voll, Beatrice Schuler-Thurner, Gerold Schuler, Niels Schaft, Stefanie Hoyer, Jan Dörrie
BACKGROUND: Merkel cell carcinoma (MCC) is a rare but very aggressive skin tumor that develops after integration of a truncated form of the large T-antigen (truncLT) of the Merkel cell polyomavirus (MCV) into the host's genome. Therapeutic vaccination with dendritic cells (DCs) loaded with tumor antigens is an active form of immunotherapy, which intends to direct the immune system towards tumors which express the respective vaccination antigens. METHODS: Cytokine-matured monocyte-derived DCs of healthy donors and MCC patients were electroporated with mRNA encoding the truncLT...
July 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28716484/the-anti-tumor-activity-of-the-stat3-inhibitor-stx-0119-occurs-via-promotion-of-tumor-infiltrating-lymphocyte-accumulation-in-temozolomide-resistant-glioblastoma-cell-line
#4
Yasuto Akiyama, Chizu Nonomura, Tadashi Ashizawa, Akira Iizuka, Ryota Kondou, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Akira Asai, Mamoru Ito, Yoshio Kiyohara, Ken Yamaguchi
STAT3 is considered to be a key molecule to mediating tumor-induced immunosuppression in various manners at tumor sites, by acting through immune-regulatory cytokines derived from the tumor cells. Specific anti-STAT3 inhibitors have been developed using nude mouse models transplanted with human tumor cells. However, mouse systems cannot accurately represent the human immune response induced by STAT3 inhibitors, and more humanized therapeutic model based on human immune cells and tumors are needed. In the present study, an immune-deficient NOG mouse with the deletion of both MHC-class I and class II genes, an MHC-double knockout mouse (dKO-NOG), was developed and used to establish humanized immunotherapeutic model...
July 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28715277/superantigen-staphylococcal-enterotoxin-c1-inhibits-the-growth-of-bladder-cancer
#5
Tao Liu, Lin Li, Lei Yin, Hongyuan Yu, Hongwei Jing, Yang Liu, Chuize Kong, Mingkai Xu
Superantigens can induce cell-mediated cytotoxicity preferentially against MHC II-positive target cells with large amounts of inflammatory cytokines releasing. In this study, superantigen staphylococcal enterotoxin C (SEC) 1 was investigated to evaluate its potential in bladder cancer immunotherapy in vitro and in vivo. Our results revealed that SEC1 could stimulate the proliferation of human peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner, accompanied with the release of interleukin-2, interferon-γ, and tumor necrosis factor-α, and increased the population of CD4(+) T cells and CD8(+) T cells...
July 17, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28714192/secreted-tumor-antigens-immune-biomarkers-for-diagnosis-and-therapy
#6
REVIEW
Els N Meeusen, Elgene Lim, Suresh Mathivanan
With the advent of immunotherapies for cancer, there is growing interest in the identification of tumor antigens. Tumor antigens are self-molecules altered through genetic mutations (neoantigens), protein truncation, protein misfolding or abnormal post translational modifications. To induce an immune response, tumor antigens need to be secreted into the tumor environment and presented to the immune system in the draining lymph nodes, resulting in the generation of tumor-specific effector cells and antibodies...
July 17, 2017: Proteomics
https://www.readbyqxmd.com/read/28710434/modifying-dendritic-cell-activation-with-plasmonic-nano-vectors
#7
Kieng Bao Vang, Ingrid Safina, Emilie Darrigues, Dmitry Nedosekin, Zeid A Nima, Waqar Majeed, Fumiya Watanabe, Ganesh Kannarpady, Rajshekhar A Kore, Daniel Casciano, Vladimir P Zharov, Robert J Griffin, Ruud P M Dings, Alexandru S Biris
Dendritic cells (DCs) can acquire, process, and present antigens to T-cells to induce an immune response. For this reason, targeting cancer antigens to DCs in order to cause an immune response against cancer is an emerging area of nanomedicine that has the potential to redefine the way certain cancers are treated. The use of plasmonically active silver-coated gold nanorods (henceforth referred to as plasmonic nano vectors (PNVs)) as potential carriers for DC tumor vaccines has not been presented before. Effective carriers must be able to be phagocytized by DCs, present low toxicity, and induce the maturation of DCs-an early indication of an immune response...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709804/identification-of-natural-regulatory-t-cell-epitopes-reveals-convergence-on-a-dominant-autoantigen
#8
John D Leonard, Dana C Gilmore, Thamotharampillai Dileepan, Wioletta I Nawrocka, Jaime L Chao, Mary H Schoenbach, Marc K Jenkins, Erin J Adams, Peter A Savage
Regulatory T (Treg) cells expressing the transcription factor Foxp3 are critical for the prevention of autoimmunity and the suppression of anti-tumor immunity. The major self-antigens recognized by Treg cells remain undefined, representing a substantial barrier to the understanding of immune regulation. Here, we have identified natural Treg cell ligands in mice. We found that two recurrent Treg cell clones, one prevalent in prostate tumors and the other associated with prostatic autoimmune lesions, recognized distinct non-overlapping MHC-class-II-restricted peptides derived from the same prostate-specific protein...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28708284/cd20-specific-immunoligands-engaging-nkg2d-enhance-%C3%AE-%C3%AE-t-cell-mediated-lysis-of-lymphoma-cells
#9
Matthias Peipp, Daniela Wesch, Hans-Heinrich Oberg, Sebastian Lutz, Anja Muskulus, Jan G J van de Winkel, Paul W H I Parren, Renate Burger, Andreas Humpe, Dieter Kabelitz, Martin Gramatzki, Christian Kellner
Human γδ T cells are innate-like T cells which are able to kill a broad range of tumor cells and thus may have potential for cancer immunotherapy. The activating receptor natural killer group 2 member D (NKG2D) plays a key role in regulating immune responses driven by γδ T cells. Here, we explored whether recombinant immunoligands consisting of a CD20 single-chain fragment variable (scFv) linked to a NKG2D ligand, either MHC class I chain-related protein A (MICA) or UL16 binding protein 2 (ULBP2), could be employed to engage γδ T cells for tumor cell killing...
July 14, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28701589/dlgr2-knockdown-boosts-dendritic-cell-activity-and-inhibits-hepatocellular-carcinoma-tumor-in-situ-growth
#10
Zhen Lu, Yun-Hong Xia, Min Zhao, Bing Zhang, Wen-Ting Dai, Lu Ding, Li-Xia Hu, Jin-Ling Bi, Guo-Lin Jiang
Tumor-specific hepatic stellate cells (tHSCs) positively participate in human hepatocellular carcinoma (HCC) tumorigenesis and progression. Our previous studies have shown that tHSCs co-culture with dendritic cells (DCs) induced DIgR2 (dendritic cell-derived immunoglobulin receptor 2) expression. The latter is a member of IgSF inhibitory receptor suppressing DCs-initiated antigen-specific T-cell responses. In the current study, we show that hepatic artery injection of DlgR2 siRNA significantly inhibited in-situ HCC xenograft growth in rat livers...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699110/immune-selection-during-tumor-checkpoint-inhibition-therapy-paves-way-for-nk-cell-missing-self-recognition
#11
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/28698147/rip2-deficiency-attenuates-cardiac-hypertrophy-inflammation-and-fibrosis-in-pressure-overload-induced-mice
#12
Cui-Hua Zhao, Xiang Ma, Hong-Yu Guo, Peng Li, Hong-Yang Liu
Although the pathological cardiac hypertrophy presents a leading cause of morbidity and mortality worldwide, our knowledge of the molecular mechanisms underlying the disease is still poor. Here, we reported that receptor-interacting serine/threonine-protein kinase 2 (RIP2), promoting pro-inflammatory gene expression, enhanced the pathological cardiac hypertrophy in animals. The effects of RIP2 on the cardiac hypertrophy triggered by pathological stimuli have not been fully investigated. In our study, mice were subjected to aortic banding (AB) surgery to explore the pathological, echocardiographic and molecular mechanisms...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28698120/effectiveness-of-formalin-killed-vaccines-containing-cpg-oligodeoxynucleotide-1668-adjuvants-against-vibrio-harveyi-in-orange-spotted-grouper
#13
Hai Trong Nguyen, Thuy Thi Thu Nguyen, Yi-Ting Wang, Pei-Chyi Wang, Shih-Chu Chen
Vibrio harveyi is a major bacterial pathogen that causes serious vibriosis in cultured groupers, leading to massive deaths. In this study, we evaluated the immune responses and protective efficacy of vaccines containing V. harveyi formalin-killed cells (FKC) formulated with CpG ODN 1668-enriched plasmids (p30CpG and p60CpG) in the orange-spotted grouper. Results indicated that antibody titres were remarkably increased in vaccinated fish 2 weeks post-immunisation. Expression level of major histocompatibility complex (MHC) class II, CD 8, and toll-like receptor 9 was significantly upregulated in the spleen of fish immunised with CpG ODN 1668-adjuvanted vaccines, as recorded at 6 weeks after immunisation...
July 8, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28696685/modeling-sequence-dependent-peptide-fluctuations-in-immunologic-recognition
#14
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/28694023/reactivity-toward-bifidobacterium-longum-and-enterococcus-hirae-demonstrate-robust-cd8-t-cell-response-and-better-prognosis-in-hbv-related-hepatocellular-carcinoma
#15
Yihui Rong, Zheng Dong, Zhixian Hong, Yun Jin, Wei Zhang, Bailong Zhang, Wei Mao, Huifang Kong, Chunping Wang, Bin Yang, Xudong Gao, Zhenyu Song, Susan E Green, Haihan K Song, Hongbo Wang, Yinying Lu
Recent studies suggest that several bacterial species are involved in tumor immunosurveillance and antitumor immunity. The role of bacteria in immune responses in HBV-related hepatocellular carcinoma (HCC) patients is still unknown. In this study, we examined the bacteria-reactive CD8(+) T cell response in patients with HBV-related HCC. We found that circulating CD8(+) T cells from healthy individuals demonstrated minimal or zero specificity toward a series of commensals and bacteria previously associated with antitumor effects, including Escherichia coli, Enterococcus faecium, Bifidobacterium longum, Bacteroides fragilis, and Enterococcus hirae...
July 7, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28681199/beneficial-effects-of-liraglutide-glp1-analog-in-the-hippocampal-inflammation
#16
Andre R C Barreto-Vianna, Marcia B Aguila, Carlos A Mandarim-de-Lacerda
The brain is very sensitive to metabolic dysfunctions induced by diets high in saturated fatty acids, leading to neuroinflammation. The liraglutide has been found to have neuroprotective effects. However, its neuroprotective action in a model of palmitate-induced neuroinflammation had not yet been evaluated. Mice were intracerebroventricular (ICV) infused with palmitate and received subcutaneous liraglutide. The hippocampal dentate gyrus and CA1 regions were analyzed (morphology and inflammation-related proteins in microglia and astrocyte by confocal microscopy)...
July 5, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28680742/modulation-of-mhc-class-i-surface-expression-in-b16f10-melanoma-cells-by-methylseleninic-acid
#17
Claudia Lennicke, Jette Rahn, Jürgen Bukur, Falko Hochgräfe, Ludger A Wessjohann, Rudolf Lichtenfels, Barbara Seliger
The essential trace element selenium (Se) might play a role in cancer prevention as well as for cancer therapy. Its metabolite methylselenol is able to kill cells through distinct mechanisms including induction of reactive oxygen species, DNA damage and apoptosis. Since methylselenol affects innate immune responses by modulating the expression of NKG2D ligands, the aim of this study was to determine whether the methylselenol generating compound methylseleninic acid (MSA) influences the expression of the MHC class I surface antigens and growth properties thereby reverting immune escape...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679396/identification-of-new-muc1-epitopes-using-hla-transgenic-animals-implication-for-immunomonitoring
#18
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/28666081/mhc-class-ii-alleles-influence-induction-of-pathogenic-antiphospholipid-antibodies-in-a-thrombosis-mouse-model
#19
Elizabeth Papalardo, Zurina Romay-Penabad, Rohan Willis, Premkumar Christadoss, Ana Laura Carrera-Marin, Elba Reyes-Maldonado, Rajani Rudrangi, Silvana Alfieri-Papalardo, Ethel Garcia-Latorre, Miri Blank, Silvia Pierangeli, Allan R Brasier, Emilio B Gonzalez
OBJECTIVE: Both environmental and genetic factors are important in antiphospholipid antibody(aPL) development in antiphospholipid syndrome(APS). Currently, the only available data on predisposing genetic factors have been obtained from epidemiological studies without mechanistic evidence. Therefore, we studied the influence of Major Histocompatibility Complex Class II(MHC-II) alleles on the production of aPL in an APS mouse model. METHODS: Three groups of mice: MHC-II deficient (MHC-II(-/-) ) mice, MHC-II(-/-) mice transgenic for human DQ6, DQ8 or DR4 alleles and their corresponding wild-type(WT) strains were each immunized, half with human β2 glycoprotein-I(β2 GPI) and the other half with control ovalbumin(OA) protein...
June 30, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28664991/artificial-human-antigen-presenting-cells-are-superior-to-dendritic-cells-at-inducing-cytotoxic-t-cell-responses
#20
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
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