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https://www.readbyqxmd.com/read/28344889/loss-of-tapasin-in-human-lung-and-colon-cancer-cells-and-escape-from-tumor-associated-antigen-specific-ctl-recognition
#1
Yosuke Shionoya, Takayuki Kanaseki, Sho Miyamoto, Serina Tokita, Ayumi Hongo, Yasuhiro Kikuchi, Vitaly Kochin, Kazue Watanabe, Ryota Horibe, Hiroshi Saijo, Tomohide Tsukahara, Yoshihiko Hirohashi, Hiroki Takahashi, Noriyuki Sato, Toshihiko Torigoe
Cytotoxic T-lymphocytes (CTLs) lyse target cells after recognizing the complexes of peptides and MHC class I molecules (pMHC I) on cell surfaces. Tapasin is an essential component of the peptide-loading complex (PLC) and its absence influences the surface repertoire of MHC class I peptides. In the present study, we assessed tapasin expression in 85 primary tumor lesions of non-small cell lung cancer (NSCLC) patients, demonstrating that tapasin expression positively correlated with patient survival. CD8(+) T-cell infiltration of tumor lesions was synergistically observed with tapasin expression and correlated positively with survival...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344864/an-immunogenic-wt1-derived-peptide-that-induces-t-cell-response-in-the-context-of-hla-a-02-01-and-hla-a-24-02-molecules
#2
Tao Dao, Tatyana Korontsvit, Victoria Zakhaleva, Casey Jarvis, Patrizia Mondello, Claire Oh, David A Scheinberg
The Wilms' tumor oncogene protein (WT1) is a highly validated tumor antigen for immunotherapy. WT1-targeted immunotherapy has been extensively explored in multiple human trials in various cancers. However, clinical investigations using WT1 epitopes have generally focused on two peptides, HLA-restricted to HLA-A*02:01 or HLA-A*24:02. The goal of this study was to identify new epitopes derived from WT1, to expand the potential use of WT1 as a target of immunotherapy. Using computer-based MHC-binding algorithms and in vitro validation of the T cell responses specific for the identified peptides, we found that a recently identified HLA-A*24:02-binding epitope (239-247), NQMNLGATL (NQM), was also a strong CD8(+) T cell epitope for HLA-A*02:01 molecule...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28341563/avoidance-of-on-target-off-tumor-activation-using-a-co-stimulation-only-chimeric-antigen-receptor
#3
Jonathan Fisher, Pierre Abramowski, Nisansala Dilrukshi Wisidagamage Don, Barry Flutter, Anna Capsomidis, Gordon Weng-Kit Cheung, Kenth Gustafsson, John Anderson
Chimeric antigen receptors (CARs) combine T cell activation with antibody-mediated tumor antigen specificity, bypassing the need for T cell receptor (TCR) ligation. A limitation of CAR technology is on-target off-tumor toxicity caused by target antigen expression on normal cells. Using GD2 as a model cancer antigen, we hypothesized that this could be minimized by using T cells expressing Vγ9Vδ2 TCR, which recognizes transformed cells in a major histocompatibility complex (MHC)-unrestricted manner, in combination with a co-stimulatory CAR that would function independently of the TCR...
March 21, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28341226/lung-adenocarcinoma-and-squamous-cell-carcinoma-gene-expression-subtypes-demonstrate-significant-differences-in-tumor-immune-landscape
#4
Hawazin Faruki, Gregory M Mayhew, Jonathan S Serody, D Neil Hayes, Charles M Perou, Myla Lai-Goldman
INTRODUCTION: Molecular subtyping of lung Adenocarcinoma (AD) and lung Squamous Cell Carcinoma (SQ) reveal biologically diverse tumors that vary in their genomic and clinical attributes. METHODS: Using published immune cell signatures and several Lung AD and SQ gene expression datasets including The Cancer Genome Atlas (TCGA), immune response in relation to AD and SQ expression subtypes was examined. Expression of immune cell populations and other immune related genes including CD274 (PD-L1) was investigated in the tumor microenvironment relative to the expression subtypes of AD (Terminal Respiratory Unit (TRU), Proximal Proliferative (PP), and Proximal Inflammatory (PI)) and SQ subtypes (Primitive, Classical, Secretory, Basal)...
March 21, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28337197/hypofractionated-irradiation-has-immune-stimulatory-potential-and-induces-a-timely-restricted-infiltration-of-immune-cells-in-colon-cancer-tumors
#5
Benjamin Frey, Michael Rückert, Julia Weber, Xaver Mayr, Anja Derer, Michael Lotter, Christoph Bert, Franz Rödel, Rainer Fietkau, Udo S Gaipl
In addition to locally controlling the tumor, hypofractionated radiotherapy (RT) particularly aims to activate immune cells in the RT-modified microenvironment. Therefore, we examined whether hypofractionated RT can activate dendritic cells (DCs), induce immune cell infiltration in tumors, and how the chronology of immune cell migration into tumors occurs to gain knowledge for future definition of radiation breaks and inclusion of immunotherapy. Colorectal cancer treatments offer only limited survival benefit, and immunobiological principles for additional therapies need to be explored with preclinical models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28320776/epigenomic-promoter-alterations-amplify-gene-isoform-and-immunogenic-diversity-in-gastric-adenocarcinoma
#6
Aditi Qamra, Manjie Xing, Nisha Padmanabhan, Jeffrey Jun Ting Kwok, Shenli Zhang, Xu Chang, Yan Shan Leong, Ai Ping Lee Lim, Qianqao Tang, WenFong Ooi, Joyce Suling Lin, Tannistha Nandi, Xiaosai Yao, Xuewen Ong, Minghui Lee, Su Ting Tay, Angie Tan Lay Keng, Erna Gondo Santoso, Cedric Chuan Young Ng, Alvin Ng, Apinya Jusakul, Duane Smoot, Hassan Ashktorab, Sun Young Rha, Khay Guan Yeoh, Wei Peng Yong, Pierce K H Chow, Weng Hoong Chan, Hock Soo Ong, Khee Chee Soo, Kyoung-Mee Kim, Wai Keong Wong, Steven G Rozen, Bin Tean Teh, Dennis Kappei, Jeeyun Lee, John Connolly, Patrick Tan
Promoter elements play important roles in isoform and cell-type specific expression. We surveyed the epigenomic promoter landscape of gastric adenocarcinoma (GC), analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) of primary GCs, GC lines, and non-malignant gastric tissues. We identified ~2000 promoter alterations (somatic promoters), many deregulated in various epithelial malignancies and mapping frequently to alternative promoters within the same gene, generating potential pro-oncogenic isoforms (RASA3)...
March 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28303769/neoepitopes-as-cancer-immunotherapy-targets-key-challenges-and-opportunities
#7
Cory A Brennick, Mariam M George, William L Corwin, Pramod K Srivastava, Hakimeh Ebrahimi-Nik
Over the last half century, it has become well established that cancers can elicit a host immune response that can target them with high specificity. Only within the last decade, with the advances in high-throughput gene sequencing and bioinformatics approaches, are we now on the forefront of harnessing the host's immune system to treat cancer. Recently, some strides have been taken toward understanding effective tumor-specific MHC I restricted epitopes or neoepitopes. However, many fundamental questions still remain to be addressed before this therapy can live up to its full clinical potential...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28301575/generation-of-murine-tumor-cell-lines-deficient-in-mhc-molecule-surface-expression-using-the-crispr-cas9-system
#8
Krishna Das, David Eisel, Clarissa Lenkl, Ashish Goyal, Sven Diederichs, Elke Dickes, Wolfram Osen, Stefan B Eichmüller
In this study, the CRISPR/Cas9 technology was used to establish murine tumor cell lines, devoid of MHC I or MHC II surface expression, respectively. The melanoma cell line B16F10 and the murine breast cancer cell line EO-771, the latter stably expressing the tumor antigen NY-BR-1 (EO-NY), were transfected with an expression plasmid encoding a β2m-specific single guide (sg)RNA and Cas9. The resulting MHC I negative cells were sorted by flow cytometry to obtain single cell clones, and loss of susceptibility of peptide pulsed MHC I negative clones to peptide-specific CTL recognition was determined by IFNγ ELISpot assay...
2017: PloS One
https://www.readbyqxmd.com/read/28298179/preparation-of-peptide-mhc-and-t-cell-receptor-dextramers-by-biotinylated-dextran-doping
#9
Michael T Bethune, Begoña Comin-Anduix, Yu-Hsien Hwang Fu, Antoni Ribas, David Baltimore
Peptide-major histocompatibility complex (pMHC) multimers enable the detection, characterization, and isolation of antigen-specific T-cell subsets at the single-cell level via flow cytometry and fluorescence microscopy. These labeling reagents exploit a multivalent scaffold to increase the avidity of individually weak T-cell receptor (TCR)-pMHC interactions. Dextramers are an improvement over the original streptavidin-based tetramer technology because they are more multivalent, improving sensitivity for rare, low-avidity T cells, including self/tumor-reactive clones...
March 1, 2017: BioTechniques
https://www.readbyqxmd.com/read/28294381/cd3-cd8-nkg2d-t-lymphocytes-induce-apoptosis-and-necroptosis-in-hla-negative-cells-via-fasl-fas-interaction
#10
O K Ivanova, T N Sharapova, E A Romanova, L P Sashchenko, D V Yashin
An important problem in cellular immunology is to identify new populations of cytotoxic lymphocytes capable of killing tumor cells that have lost classical components of MHC-machinery and to understand mechanisms of the death of these cells. We have previously found that CD4(+) CD25(+) lymphocytes appear in the lymphokine-activated killer (LAK) cell culture, which carry Tag7 (PGRP-S) and FasL proteins on their surface and can kill Hsp70- and Fas-expressing HLA-negative cells. In this work, we have continued to study the mechanisms of killing of the HLA-negative tumor cells, focusing this time on the CD8+ lymphocytes...
March 15, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28294313/suppression-of-murine-tumor-growth-through-cd8-ctls-via-activated-dec-205-dendritic-cells-by-sequential-administration-of-%C3%AE-galactosylceramide-in-vivo
#11
Hideki Kogo, Masumi Shimizu, Yasuyuki Negishi, Eiji Uchida, Hidemi Takahashi
Cancer immunity is mediated through the effective priming and activation of tumor-specific class I major histocompatibility complex (MHC-I) molecule-restricted CD8(+) cytotoxic T lymphocytes (CTLs). DEC-205(+) dendritic cells (DCs) can cross-present the epitope(s) of captured tumor antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumor-specific CD8(+) CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of impaired CTL induction...
March 12, 2017: Immunology
https://www.readbyqxmd.com/read/28287848/immunomodulating-and-immunoresistance-properties-of-cancer-initiating-cells-implications-for-the-clinical-success-of-immunotherapy
#12
Cristina Maccalli, Giorgio Parmiani, Soldano Ferrone
Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth...
March 13, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28284008/effective-and-persistent-antitumor-activity-of-her2-directed-car-t-cells-against-gastric-cancer-cells-in-vitro-and-xenotransplanted-tumors-in-vivo
#13
Yanjing Song, Chuan Tong, Yao Wang, Yunhe Gao, Hanren Dai, Yelei Guo, Xudong Zhao, Yi Wang, Zizheng Wang, Weidong Han, Lin Chen
Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties...
March 10, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28278221/antitumor-activity-of-orally-administered-maitake-%C3%AE-glucan-by-stimulating-antitumor-immune-response-in-murine-tumor
#14
Yuki Masuda, Yoshiaki Nakayama, Akihiro Tanaka, Kenta Naito, Morichika Konishi
Maitake α-glucan, YM-2A, isolated from Grifola frondosa, has been characterized as a highly α-1,6-branched α-1,4 glucan. YM-2A has been shown to possess an anti-virus effect in mice; however, it does not directly inhibit growth of the virus in vitro, indicating that the anti-virus effect of YM-2A might be associated with modulation of the host immune system. In this study, we found that oral administration of YM-2A could inhibit tumor growth and improve survival rate in two distinct mouse models of colon-26 carcinoma and B16 melanoma...
2017: PloS One
https://www.readbyqxmd.com/read/28266500/absence-of-pd-l1-on-tumor-cells-is-associated-with-reduced-mhc-i-expression-and-pd-l1-expression-increases-in-recurrent-serous-ovarian-cancer
#15
Stefanie Aust, Sophie Felix, Katharina Auer, Anna Bachmayr-Heyda, Lukas Kenner, Sabine Dekan, Samuel M Meier, Christopher Gerner, Christoph Grimm, Dietmar Pils
Immune-evasion and immune checkpoints are promising new therapeutic targets for several cancer entities. In ovarian cancer, the clinical role of programmed cell death receptor ligand 1 (PD-L1) expression as mechanism to escape immune recognition has not been clarified yet. We analyzed PD-L1 expression of primary ovarian and peritoneal tumor tissues together with several other parameters (whole transcriptomes of isolated tumor cells, local and systemic immune cells, systemic cytokines and metabolites) and compared PD-L1 expression between primary tumor and tumor recurrences...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28260295/-experimental-study-on-the-immune-response-of-fusion-tumor-vaccine-of-hepg2-and-dendritic-cells-in-vitro
#16
Y B Pang, B Y Cui, J He, X P Huang, W Liang, L Q Li, X L Luo
Objective: To estimate the immune response of HepG2/dendritic cell (DC) fusion cells vaccines against HepG2 cells in vitro. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors by Ficoll-Hypaque density-gradient centrifugation.Then DC were obtain from PBMCs by culturing in medium containing granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 5 days.DC and HepG2 fusion cells were induced by polythyleneglycol (PEG). The fusion cells were examined under fluorescence microscope by labeling DCs and HepG2 with green and red fluorescein, respectively, and then the fusion rates were analyzed by flow cytometry...
February 21, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28254787/serine-proteases-enhance-immunogenic-antigen-presentation-on-lung-cancer-cells
#17
Haley L Peters, Satyendra C Tripathi, Celine Kerros, Hiroyuki Katayama, Haven R Garber, Lisa S St John, Lorenzo Federico, Ismail M Meraz, Jack A Roth, Boris Sepesi, Mourad Majidi, Kathryn Ruisaard, Karen Clise-Dwyer, Jason Roszik, Don L Gibbons, John Heymach, Stephen G Swisher, Chantale Bernantchez, Gheath Alatrash, Samir M Hanash, Jeffrey J Molldrem
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these re-invigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3...
March 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28243692/intratumoral-administration-of-cgamp-transiently-accumulates-potent-macrophages-for-anti-tumor-immunity-at-a-mouse-tumor-site
#18
Takayuki Ohkuri, Akemi Kosaka, Kei Ishibashi, Takumi Kumai, Yui Hirata, Kenzo Ohara, Toshihiro Nagato, Kensuke Oikawa, Naoko Aoki, Yasuaki Harabuchi, Esteban Celis, Hiroya Kobayashi
Stimulator of IFN genes (STING) spontaneously contributes to anti-tumor immunity by inducing type I interferons (IFNs) following sensing of tumor-derived genomic DNAs in the tumor-bearing host. Although direct injection of STING ligands such as cyclic diguanylate monophosphate (c-di-GMP) and cyclic [G(2',5')pA(3',5')p] (cGAMP) into the tumor microenvironment exerts anti-tumor effects through strong induction of type I IFNs and activation of innate and adaptive immunity, the precise events caused by STING in the tumor microenvironment remain to be elucidated...
February 27, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28238951/oral-administration-of-the-nitroxide-radical-tempol-exhibits-immunomodulatory-and-therapeutic-properties-in-multiple-sclerosis-models
#19
Sarah Neil, Jaebong Huh, Victoria Baronas, Xinhui Li, Henry F McFarland, Murali Cherukuri, James B Mitchell, Jacqueline A Quandt
Therapies with both immunomodulatory and neuroprotective properties are thought to have the greatest promise in reducing the severity and progression of multiple sclerosis (MS). Several reactive oxygen (ROS) and reactive nitrogen species (RNS) are implicated in inflammatory-mediated damage to the central nervous system (CNS) in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) is a stable nitroxide radical with potent antioxidant activity...
February 24, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28238782/vaccination-efficacy-with-marrow-mesenchymal-stem-cell-against-cancer-was-enhanced-under-simulated-microgravity
#20
Jing Li, Jun Chen, Xiuyu Li, Yanfang Qian
Stem cell vaccination can induce consistent and strong anti-tumor immunity against cancer in mice model. The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine MSCs. Based on this conception, we first compared their tumor vaccines intervention effects of adult MSCs and MSCs under simulated microgravity (MSC/SMG)...
April 8, 2017: Biochemical and Biophysical Research Communications
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