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MHC tumor

Lei Zhang, Jie Ren, Peidian Shi, Dong Lu, Chengxue Zhao, Yanxin Su, Lilin Zhang, Jinhai Huang
B4GALT5, also known as β-1, 4 galactosyltransferase V, is one of the members of β-1, 4 galactosyltransferase gene (B4GALT) family, which was concerned with embryonic development, tumor generation, other malignant diseases. In this study, we firstly cloned porcine B4GALT (pB4GALT5) from porcine alveolar macrophages, and predicted the structural domain and function of seven porcine β-1, 4 galactosyltransferase (I-VII) based on transcriptome analysis of PRRSV infected cells. Additionally, the upregulated porcine B4GALT5 expression was detected from PRRSV infected porcine alveolar macrophage (PAM) cells...
2018: Frontiers in Cellular and Infection Microbiology
Dinler A Antunes, Didier Devaurs, Mark Moll, Gregory Lizée, Lydia E Kavraki
The class I major histocompatibility complex (MHC) is capable of binding peptides derived from intracellular proteins and displaying them at the cell surface. The recognition of these peptide-MHC (pMHC) complexes by T-cells is the cornerstone of cellular immunity, enabling the elimination of infected or tumoral cells. T-cell-based immunotherapies against cancer, which leverage this mechanism, can greatly benefit from structural analyses of pMHC complexes. Several attempts have been made to use molecular docking for such analyses, but pMHC structure remains too challenging for even state-of-the-art docking tools...
March 12, 2018: Scientific Reports
Jie Wang, Lina Yang, Xiaohe Mao, Zaiye Li, Xiaoyu Lin, Canhua Jiang
It has been shown that the peripheral blood mononuclear cells (PBMCs) from oral squamous cell carcinoma (OSCC) patients presented cytotoxic CD8 T cell response against Streptococcus salivarius (S. salivarius), of which the frequency was positively associated with recurrence-free survival in OSCC patients. To identify the conditions required for regulating S. salivarius-specific CD8 T cell-mediated cytotoxicity, we selectively depleted individual components of the PBMCs, and observed that the depletion of monocytes/macrophages, but not other immune cell subsets, significantly downregulated the S...
March 9, 2018: Experimental Cell Research
Tong Wang, Fumou Sun, Yang Wang, Jiahao Jiang, Mingzhu Pan, Minne Yuan, Hang Zhang, Xiaodian Du, Kamal Hezam, Kai Song, Min Wang, Juan Zhang
Colorectal carcinoma (CRC) is one of the most common malignant cancers worldwide. The poor response of CRC to chemotherapy has whipped up the interest in targeted therapy with monoclonal antibodies for its potential efficiency. However, cetuximab, as one of the first-line targeted drugs in the treatment of CRC, has drug resistance and poor prognosis in clinic. To address this, a novel bispecific protein with CRC targeting and natural killer (NK) cell triggering was used for treatment. NK cell-mediated immunosurveillance is normally activated by the activating receptor natural killer cell receptor NK group 2, member D (NKG2D), which binds its key ligand major histocompatibility complex (MHC) class I-related chain A (MICA) expressed on the tumor cells...
April 2018: Journal of Immunotherapy
Ruth Pye, Amanda Patchett, Elspeth McLennan, Russell Thomson, Scott Carver, Samantha Fox, David Pemberton, Alexandre Kreiss, Adriana Baz Morelli, Anabel Silva, Martin J Pearse, Lynn M Corcoran, Katherine Belov, Carolyn J Hogg, Gregory M Woods, A Bruce Lyons
Devil facial tumor disease (DFTD) is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I) on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government's Wild Devil Recovery project...
2018: Frontiers in Immunology
Miseon Lee, In Hye Song, Sun-Hee Heo, Young-Ae Kim, In Ah Park, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Purpose: In the presence of interferon, proteasome subunits are replaced by their inducible counterparts to form an immunoproteasome (IP) plays a key role in generation of antigenic peptides presented by MHC class I molecules, leading to elicitation of a T cell‒mediated immune response. Although the roles of IP in other cancers, and inflammatory diseases have been extensively studied, its significance in breast cancer is unclear. Materials and Methods: We investigated the expression of LMP7, an IP subunit, and its relationship with immune system components in two breast cancer cohorts...
February 26, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Ida Hafstrand, Elien M Doorduijn, Renhua Sun, Anna Talyzina, Marjolein Sluijter, Sara Pellegrino, Tatyana Sandalova, Adil Doganay Duru, Thorbald van Hall, Adnane Achour
Human cancers frequently display defects in Ag processing and presentation allowing for immune evasion, and they therefore constitute a significant challenge for T cell-based immunotherapy. We have previously demonstrated that the antigenicity of tumor-associated Ags can be significantly enhanced through unconventional residue modifications as a novel tool for MHC class I (MHC-I)-based immunotherapy approaches. We have also previously identified a novel category of cancer neo-epitopes, that is, T cell epitopes associated with impaired peptide processing (TEIPP), that are selectively presented by MHC-I on cells lacking the peptide transporter TAP...
March 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Moniek A de Witte, Dhifaf Sarhan, Zachary Davis, Martin Felices, Daniel A Vallera, Peter Hinderlie, Julie Curtsinger, Sarah Cooley, John Wagner, Jurgen Kuball, Jeffrey S Miller
Relapse is the most frequent cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HCT). NK cells and γδ T cells reconstitute early after allo-HCT, contribute to tumor immunosurveillance via MHC independent mechanisms and do not induce graft-versus-host disease (GVHD). Here we performed a quantitative and qualitative analysis of the NK and γδ T cell repertoire in healthy individuals, recipients of HLA-matched sibling or unrelated donor allo-HCT (MSD/MUD-HCT) and umbilical cord blood-HCT (UCB-HCT)...
March 2, 2018: Biology of Blood and Marrow Transplantation
Anne C Knol, Jean-Michel Nguyen, Marie-Christine Pandolfino, Marc G Denis, Amir Khammari, Brigitte Dréno
Prognostic biomarkers for melanoma patients after lymph node resection are of clinical relevance and could thus enable the identification of patients who therefore would most benefit from adjuvant treatment. The aim of this work was to determine, using an in vitro model, whether immune-related biomarkers such as MHC-class I and II, melanoma associated antigens, IDO1 and PD-L1, could also be relevant to predict the risk of relapse of stage III melanoma patients after lymph node resection. We established tumor cell lines from metastatic lymph nodes of 50 melanoma patients...
March 5, 2018: Experimental Dermatology
Alexander Bagaev, Aleksey Pichugin, Edward L Nelson, Michael G Agadjanyan, Anahit Ghochikyan, Ravshan I Ataullakhanov
Dendritic cells (DCs) are well-known for their functions in orchestrating the innate and adaptive arms of immune defense. However, under certain conditions, DCs can exert tumoricidal activity. We have elucidated the mechanism of tumor suppression by TLR4-activated bone marrow-derived DCs (BMDCs) isolated from BALB/c mice. We identified that two distinct subsets of BMDCs (CD11b+ CD11c+ I-A/Eint and CD11b+ CD11c+ I-A/Ehigh ) have different cytotoxic mechanisms of action. The cytotoxicity of the former subset is mediated through NO and reactive oxygen species and type I IFN (IFN-β), whereas the latter subset acts only through IFN-β...
March 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Jooeun Bae, Teru Hideshima, Yu-Tzu Tai, Yan Song, Paul Richardson, Noopur Raje, Nikhil C Munshi, Kenneth C Anderson
Histone deacetylases (HDAC) are therapeutic targets in multiple cancers. ACY241, an HDAC6 selective inhibitor, has shown anti-multiple myeloma (MM) activity in combination with immunomodulatory drugs and proteasome inhibitors. Here we show ACY241 significantly reduces the frequency of CD138+ MM cells, CD4+ CD25+ FoxP3+ regulatory T cells, and HLA-DRLow/- CD11b+ CD33+ myeloid-derived suppressor cells; and decreases expression of PD1/PD-L1 on CD8+ T cells and of immune checkpoints in bone marrow cells from myeloma patients...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Cristina Rius, Meriem Attaf, Katie Tungatt, Valentina Bianchi, Mateusz Legut, Amandine Bovay, Marco Donia, Per Thor Straten, Mark Peakman, Inge Marie Svane, Sascha Ott, Tom Connor, Barbara Szomolay, Garry Dolton, Andrew K Sewell
Peptide-MHC (pMHC) multimers, usually used as streptavidin-based tetramers, have transformed the study of Ag-specific T cells by allowing direct detection, phenotyping, and enumeration within polyclonal T cell populations. These reagents are now a standard part of the immunology toolkit and have been used in many thousands of published studies. Unfortunately, the TCR-affinity threshold required for staining with standard pMHC multimer protocols is higher than that required for efficient T cell activation. This discrepancy makes it possible for pMHC multimer staining to miss fully functional T cells, especially where low-affinity TCRs predominate, such as in MHC class II-restricted responses or those directed against self-antigens...
February 26, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Danping Hong, Jiongyan Ding, Ouyang Li, Quan He, Minxia Ke, Mengyi Zhu, Lili Liu, Wen-Bin Ou, Yulong He, Yuehong Wu
BACKGROUND: Induced pluripotent stem cells (iPS) represent an innovative source for the standardized in vitro generation of macrophages (Mφ). Mφ show great promise in disease pathogenesis, particularly tuberculosis. However, there is no information about human iPS-derived (hiPS) macrophages (hiPS-Mφ) in response to tuberculosis infection. METHODS: In the present study, macrophages derived from hiPS were established via embryoid body (EB) formation by using feeder-free culture conditions, and the human monocyte cell line THP-1 (THP-1-Mφ) was used as control...
February 26, 2018: Stem Cell Research & Therapy
Hyunjoon Kim, Lin Niu, Peter Larson, Tamara A Kucaba, Katherine A Murphy, Britnie R James, David M Ferguson, Thomas S Griffith, Jayanth Panyam
Cytotoxic T lymphocytes (CTLs) play a major role in cancer immunotherapy because of their ability to directly kill tumor cells and secrete tumor suppressive cytokines. Anticancer vaccines aim to provoke tumor-specific CTL responses, which require activation of antigen presenting cells (APCs) including dendritic cells (DCs) and macrophages. Therefore, a potent immunostimulatory adjuvant capable of activating APCs is an essential component of anticancer vaccines. In this study, we introduce novel TLR 7/8 bi-specific agonists that significantly enhance cytokine secretion compared to TLR7 mono-selective compounds...
February 17, 2018: Biomaterials
Guang Shan, Tian Tang, Huijun Qian, Yue Xia
A subset of bladder patients does not respond to BCG treatment effectively and the underlying reason behind this observation is currently unclear. CD4+ T cells are composed of various subsets that each expresses a distinctive set of cytokines and can potently shift the immune response toward various directions. In this study, we examined the CD4+ T-cell cytokine response in bladder cancer patients toward BCG stimulation. We found that bladder cancer patients presented a variety of responses toward BCG, with no uniform characteristics...
February 24, 2018: Cancer Immunology, Immunotherapy: CII
Long Liu, Ying-Jun Chang, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Kai-Yan Liu, Xiao-Jun Huang
Acute B lymphoblastic leukemia (B-ALL) relapse contributes predominantly to the mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the mechanism of B-ALL relapse after allo-HSCT remains unknown. The eradication of leukemia after allo-HSCT largely relies on graft-versus-leukemia (GVL) effects mediated by donor T cells. T cell exhaustion, characterized by the increased expression of inhibitory receptors and impaired function, may suppress GVL effects. In this study, we evaluated whether T cell exhaustion was involved in B-ALL relapse after allo-HSCT...
February 22, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Christina Klasen, Tamar Ziehm, Michael Huber, Yaw Asare, Aphrodite Kapurniotu, Idit Shachar, Jürgen Bernhagen, Omar El Bounkari
Macrophage migration inhibitory factor (MIF) is a chemokine-like inflammatory cytokine, which plays a pivotal role in the pathogenesis of inflammatory and cardiovascular diseases as well as cancer. We previously identified MIF as a novel B cell chemokine that promotes B cell migration through non-cognate interaction with the CXC chemokine receptor CXCR4 and CD74, the surface form of MHC class II invariant chain. In this study, we have analyzed the regulation of the MIF receptors under inflammatory conditions by investigating the impact of lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) on CD74 and CXCR4 expression in B lymphocytes...
February 21, 2018: Cellular Signalling
Kiyomi Shitaoka, Hiroshi Hamana, Hiroyuki Kishi, Yoshihiro Hayakawa, Eiji Kobayashi, Kenta Sukegawa, Xiuhong Piao, Fulian Lyu, Takuya Nagata, Daisuke Sugiyama, Hiroyoshi Nishikawa, Atsushi Tanemura, Ichiro Katayama, Mutsunori Murahashi, Yasushi Takamatsu, Kenzaburo Tani, Tatsuhiko Ozawa, Atsushi Muraguchi
T-cell receptor (TCR) gene therapy is a promising next-generation antitumor treatment. We previously developed a single-T-cell analysis protocol that allows the rapid capture of paired TCRalpha and beta cDNAs. Here, we applied the protocol to analyze the TCR repertoire of tumor-infiltrating lymphocytes (TILs) of various cancer patients. We found clonally expanded populations of T cells that expressed the same clonotypic TCR in 50 to 70% of CD137+CD8+ TILs, indicating that they responded to certain antigens in the tumor environment...
February 23, 2018: Cancer Immunology Research
S M Mansour Haeryfar, Christopher R Shaler, Patrick T Rudak
Mucosa-associated invariant T (MAIT) cells are a subset of innate-like T lymphocytes known for their ability to respond to MHC-related protein 1 (MR1)-restricted stimuli and select cytokine signals. They are abundant in humans and especially enriched in mucosal layers, common sites of neoplastic transformation. MAIT cells have been found within primary and metastatic tumors. However, whether they promote malignancy or contribute to anticancer immunity is unclear. On the one hand, MAIT cells produce IL-17A in certain locations and under certain circumstances, which could in turn facilitate neoangiogenesis, intratumoral accumulation of immunosuppressive cell populations, and cancer progression...
February 22, 2018: Cancer Immunology, Immunotherapy: CII
Marie Indrová, Joanna Rossowska, Elzbieta Pajtasz-Piasecka, Romana Mikyšková, Jan Richter, Jozef Rosina, Radislav Sedlacek, Anna Fišerová
The present study aimed to elucidate the role of cluster of differentiation (CD)8+, CD4+, natural killer (NK), and myeloid (CD11b+) cells in the course of the growth and rejection of experimental major histocompatibility complex (MHC) class I-deficient, HPV16 E6/E7-associated TC-1/A9 tumors in mice. Stable mouse lines (F30 ) generated by inbreeding of Balb/c and C57BL/6 strains, which were characterized by H-2Db+d-NK1.1neg (B6-neg) and H-2Db-d+NK1.1high (Balb-high) phenotypes, were used for the present study...
March 2018: Oncology Letters
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