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https://www.readbyqxmd.com/read/28430604/signal-transducing-adaptor-protein-2-promotes-generation-of-functional-long-term-memory-cd8-t-cells-by-preventing-terminal-effector-differentiation
#1
Daisuke Muraoka, Naohiro Seo, Tae Hayashi, Chisaki Hyuga-Amaike, Kana Okamori, Isao Tawara, Naozumi Harada, Hiroshi Shiku
Long-surviving memory CD8+ T cells generated by stimulation with appropriate tumor-associated antigens are the most aggressive and persistent tumoricidal effectors. In this event of memory CD8+ T cell development, the signal transducer and activator of transcription (STAT) proteins function as the crucial intracellular signaling molecules, but the regulatory mechanism of STATs in CD8+ T cells is not fully understood. In this study, we report for the first time, by using murine vaccination models, that signal-transducing adaptor protein-2 (STAP2) maintains the cytotoxicity of long-lived memory CD8+ T cells by controlling a STAT3/suppressor of cytokine signaling 3 (SOCS3) cascade...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430349/prognostic-significance-of-infiltrating-immune-cell-subtypes-in-invasive-ductal-carcinoma-of-the-breast
#2
Yangmei Xu, Suzhen Lan, Qiuhong Zheng
PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis. MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low)...
April 20, 2017: Tumori
https://www.readbyqxmd.com/read/28425860/a-novel-recombinant-multi-epitope-vaccine-could-induce-specific-cytotoxic-t-lymphocyte-response-in-vitro-and-in-vivo
#3
Yahong Wu, Wenjie Zhai, Meng Sun, Zhe Zou, Xiuman Zhou, Guodong Li, Zhongyi Yan, Yuanming Qi, Yanfeng Gao
Cytotoxic T lymphocytes (CTLs) against various tumor antigens play an important role in elimination of tumor cells. To develop therapeutic vaccines that can induce specific immune response, we designed a novel recombinant multiepitope vaccine YL66 which consists of HLA-A2-restricted CTL epitopes from two widely expressed tumor antigen cyclooxygenase-2 and MAGE-4, linked with membrane permeable Tat-PTD and the universal T helper epitope. The DNA fragment of YL66 was cloned into pGEX-4T-2-YL66 and pcDNA3.1(+)-YL66, respectively...
April 19, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28421385/in-vitro-and-in-vivo-anti-tumor-effects-of-selected-platinum-iv-and-dinuclear-platinum-ii-complexes-against-lung-cancer-cells
#4
Milos Arsenijevic, Marija Milovanovic, Snezana Jovanovic, Natalija Arsenijevic, Bojana Simovic Markovic, Marina Gazdic, Vladislav Volarevic
In the present study, cytotoxic effects of cisplatin, the most usually used chemotherapeutic agent, were compared with new designed platinum(IV) ([PtCl4(en)] (en = ethylenediamine) and [PtCl4(dach)]) (dach = (±)-trans-1,2-diaminocyclohexane) and platinum(II) complexes ([{trans-Pt(NH3)2Cl}2(μ-pyrazine)](ClO4)2 (Pt1), [{trans-Pt(NH3)2Cl}2(μ-4,4'-bipyridyl)](ClO4)2DMF(Pt2),[{trans-Pt(NH3)2Cl}2(μ-1,2-bis(4pyridyl)ethane)](ClO4)2 (Pt3)), in vitro and in vivo against human and murine lung cancer cells, to determine anti-tumor potential of newly synthesized platinum-based drugs in the therapy of lung cancer...
April 18, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28417012/coordinating-antigen-cytosolic-delivery-and-danger-signaling-to-program-potent-cross-priming-by-micelle-based-nanovaccine
#5
Zhida Liu, Chang Zhou, Yan Qin, Zihao Wang, Luyao Wang, Xiuli Wei, Yinjian Zhou, Qicheng Li, Hang Zhou, Wenjun Wang, Yang-Xin Fu, Mingzhao Zhu, Wei Liang
Although re-activating cytotoxic T-cell (CTLs) response inside tumor tissues by checkpoint blockade has demonstrated great success in tumor immunotherapy, active induction of efficient endogenous CTL response by therapeutic vaccines has been largely hampered by inefficient cytosolic delivery of antigens and coordinated activation of dendritic cells (DCs) in lymph nodes. Here we show that polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles transform soluble peptides into α-helix to enable their efficient cytosolic delivery...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28413216/uncompromised-nk-cell-activation-is-essential-for-virus-specific-ctl-activity-during-acute-influenza-virus-infection
#6
Yuan Liu, Jian Zheng, Yinping Liu, Liyan Wen, Lei Huang, Zheng Xiang, Kwok-Tai Lam, Aizhen Lv, Huawei Mao, Yu-Lung Lau, Wenwei Tu
Natural killer (NK) cells are indispensable components of both the innate and adaptive immune response. However, their precise roles in the cross-talk between innate and adaptive immunity during influenza virus infection remain controversial. By comparing NK cell dynamics and activity under a sub-lethal dose and high dose of influenza virus infection, we showed that influenza virus PR8 directly infected NK cells during natural infection, which was consistent with our previous findings obtained from an in vitro investigation of human NK cells...
April 17, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28412740/combination-epidermal-growth-factor-receptor-variant-iii-peptide-pulsed-dendritic-cell-vaccine-with-mir-326-results-in-enhanced-killing-on-egfrviii-positive-cells
#7
Jianlong Li, Feng Wang, Guangzhi Wang, Ying Sun, Jinquan Cai, Xing Liu, Junhe Zhang, Xiaoyan Lu, Yongli Li, Meng Chen, Lingchao Chen, Chuanlu Jiang
The mutant Type III variant of epidermal growth factor receptor (EGFRvIII) is present in approximately one-third of glioblastoma (GBM) patients. It is never found in normal tissues; therefore, it represents a candidate target for GBM immunotherapy. PEPvIII, a peptide sequence from EGFRvIII, was designed to represent a target of glioma and is presented by MHC I/II complexes. Dendritic cells (DCs) have great potential to sensitize CD4+ T and CD8+ T cells to precisely target and eradicate GBM. Here, we show that PEPvIII could be loaded by DCs and presented to T lymphocytes, especially PEPvIII-specific CTLs, to precisely kill U87-EGFRvIII cells...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410529/ifn%C3%AE-enhances-cytotoxic-efficiency-of-the-cytotoxic-t-lymphocytes-against-human-glioma-cells
#8
Shengwen Shao, Eric Risch, Danielle Burner, Lingeng Lu, Boris Minev, Wenxue Ma
Cytotoxic T lymphocytes (CTLs) are a key player in cancer immunotherapies, and MHC class I molecules on the cell surface are crucial for cellular recognition. However, the aberrant expression of MHC class I molecules is frequently found in various malignancies. IFNγ has dual functions in cancer progression, and its effect on tumor immunity is controversial. To investigate whether IFNγ can enhance cytotoxic efficiency of the tumor antigen-specific CTLs, we generated the CTLs using modified human dendritic cells as antigen presenting cells, then studied the activities of CTLs on human leukocyte antigen (HLA)-A2 positive glioma cells treated with, or without IFNγ...
April 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28407485/defective-hiv-1-proviruses-are-expressed-and-can-be-recognized-by-cytotoxic-t-lymphocytes-which-shape-the-proviral-landscape
#9
Ross A Pollack, R Brad Jones, Mihaela Pertea, Katherine M Bruner, Alyssa R Martin, Allison S Thomas, Adam A Capoferri, Subul A Beg, Szu-Han Huang, Sara Karandish, Haiping Hao, Eitan Halper-Stromberg, Patrick C Yong, Colin Kovacs, Erika Benko, Robert F Siliciano, Ya-Chi Ho
Despite antiretroviral therapy, HIV-1 persists in memory CD4(+) T cells, creating a barrier to cure. The majority of HIV-1 proviruses are defective and considered clinically irrelevant. Using cells from HIV-1-infected individuals and reconstructed patient-derived defective proviruses, we show that defective proviruses can be transcribed into RNAs that are spliced and translated. Proviruses with defective major splice donors (MSDs) can activate novel splice sites to produce HIV-1 transcripts, and cells with these proviruses can be recognized by HIV-1-specific cytotoxic T lymphocytes (CTLs)...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28405920/effector-functions-of-memory-ctls-can-be-affected-by-signals-received-during-reactivation
#10
Yingjun Lv, Elliot Mattson, Anjuli Bhadurihauck, Karla Garcia, Lei Li, Zhengguo Xiao
Memory cytotoxic T lymphocytes (CTLs) are able to provide protections to the host against repeated insults from intracellular pathogens. However, it has not been completely understood how the effector functions of memory CTLs are induced upon antigen challenge, which is directly related to the efficacy of their protection. Third signal cytokines, such as IL-12 and type I interferon, have been suggested to be involved in the protective function of memory CTLs, but direct evidence is warranted. In this report, we found that memory CTLs need to be reactivated to exert effector functions...
April 12, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28404865/dual-angiopoietin-2-and-vegfa-inhibition-elicits-antitumor-immunity-that-is-enhanced-by-pd-1-checkpoint-blockade
#11
Martina Schmittnaegel, Nicolò Rigamonti, Ece Kadioglu, Antonino Cassará, Céline Wyser Rmili, Anna Kiialainen, Yvonne Kienast, Hans-Joachim Mueller, Chia-Huey Ooi, Damya Laoui, Michele De Palma
Pathological angiogenesis is a hallmark of cancer and a therapeutic target. Vascular endothelial growth factor A (VEGFA) and angiopoietin-2 (ANGPT2; also known as ANG2) are proangiogenic cytokines that sustain tumor angiogenesis and limit antitumor immunity. We show that combined ANGPT2 and VEGFA blockade by a bispecific antibody (A2V) provided superior therapeutic benefits, as compared to the single agents, in both genetically engineered and transplant tumor models, including metastatic breast cancer (MMTV-PyMT), pancreatic neuroendocrine tumor (RIP1-Tag2), and melanoma...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28394813/transforming-growth-factor-%C3%AE-is-a-poor-prognostic-factor-and-inhibits-the-favorable-prognostic-value-of-cd8-ctl-in-human-hepatocellular-carcinoma
#12
Chun-Yu Huang, Hua Wang, Wei Liao, Feng Han, Yong-Qiang Li, Shu-Wei Chen, Xiang-Ming Lao
It is widely understood that transforming growth factor β (TGF-β) has dual functions in tumors-tumor promoter or tumor suppressor. As a tumor promoter, TGF-β drives tumor initiation and progression partially by suppressing the antitumor responses of CD8 cytotoxic T lymphocytes (CTLs) in the tumor microenvironment. Here, we investigated the prognostic value of measuring TGF-β and CD8 CTLs levels and their relationship in human hepatocellular carcinoma (HCC). Immunohistochemical staining was conducted to analyze the prognostic value of TGF-β expression and/or CD8 CTLs levels in 407 HCC patients...
April 7, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28394417/achieving-large-area-planar-perovskite-solar-cells-by-introducing-an-interfacial-compatibilizer
#13
Jinho Lee, Hongkyu Kang, Geunjin Kim, Hyungcheol Back, Junghwan Kim, Soonil Hong, Byoungwook Park, Eunhag Lee, Kwanghee Lee
Despite the recent unprecedented increase in the power conversion efficiencies (PCEs) of small-area devices (≤0.1 cm(2) ), the PCEs deteriorate drastically for PSCs of larger areas because of the incomplete film coverage caused by the dewetting of the hydrophilic perovskite precursor solutions on the hydrophobic organic charge-transport layers (CTLs). Here, an innovative method of fabricating scalable PSCs on all types of organic CTLs is reported. By introducing an amphiphilic conjugated polyelectrolyte as an interfacial compatibilizer, fabricating uniform perovskite films on large-area substrates (18...
April 10, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28390430/impact-of-the-body-mass-index-on-perioperative-immunological-disturbances-in-patients-with-hip-and-knee-arthroplasty
#14
Simon Jasinski-Bergner, Anna-Luise Radetzki, Janine Jahn, David Wohlrab, Heike Kielstein
BACKGROUND: Obesity increases the risk for knee and hip joint implantation and negatively contributes to wound healing. In this study, in 52 patients undergoing hip and knee arthroplasty the amount of peripheral immune effector cells pre- and post-operative, as well as the expression of certain soluble factors affecting the functions of immune effector cells were investigated. METHODS: The peripheral immune cells and the expression of the soluble factors were determined by flow cytometry and correlated to each other in dependency of the BMI, the sex, and the kind of arthroplasty...
April 8, 2017: Journal of Orthopaedic Surgery and Research
https://www.readbyqxmd.com/read/28383470/evaluation-of-adenosine-lidocaine-and-magnesium-for-enhancement-of-platelet-function-during-storage
#15
James A Bynum, Ashley S Taylor, Grantham C Peltier, Colby S McIntosh, Michael A Meledeo, Geoffrey P Dobson, Andrew P Cap
BACKGROUND: The combination of Adenosine, lidocaine and Mg2+ (ALM) has demonstrated cardioprotective and resuscitative properties in models of cardiac arrest and hemorrhagic shock that are linked to reduction of metabolic demand. Platelets play a key role in resuscitation strategies for ATC, but suffer from loss of function following storage in part due to mitochondrial exhaustion. This study evaluates whether ALM also demonstrates protective properties in stored platelet preparations...
April 5, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28378248/role-of-il-21-in-htlv-1-infections-with-emphasis-on-htlv-1-associated-myelopathy-tropical-spastic-paraparesis-ham-tsp
#16
Taraneh Rajaei, Hamid Farajifard, Houshang Rafatpanah, Reza Bustani, Narges Valizadeh, Bahareh Rajaei, Seyed Abdolrahim Rezaee
Interleukin-21 (IL-21) enhances the survival and cytotoxic properties of cytotoxic T cells (CTLs) and exhibits essential roles in controlling chronic viral infections. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive inflammatory disease of the nervous system. The main determinant of disease progression is efficiency of the CTL response to Human T lymphotropic virus types I (HTLV-1). In this study, the expression of host IL-21 and HTLV-I Tax and proviral load (PVL) was evaluated to understand the role and mechanism of IL-21 in HTLV-1 infections and the subsequent development of HAM/TSP...
April 4, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28374848/pathogen-recognition-of-a-novel-c-type-lectin-from-marsupenaeus-japonicus-reveals-the-divergent-sugar-binding-specificity-of-qap-motif
#17
Rod Russel R Alenton, Keiichiro Koiwai, Kohei Miyaguchi, Hidehiro Kondo, Ikuo Hirono
C-type lectins (CTLs) are calcium-dependent carbohydrate-binding proteins known to assist the innate immune system as pattern recognition receptors (PRRs). The binding specificity of CTLs lies in the motif of their carbohydrate recognition domain (CRD), the tripeptide motifs EPN and QPD bind to mannose and galactose, respectively. However, variants of these motifs were discovered including a QAP sequence reported in shrimp believed to have the same carbohydrate specificity as QPD. Here, we characterized a novel C-type lectin (MjGCTL) possessing a CRD with a QAP motif...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28367538/tracking-the-fate-and-origin-of-clinically-relevant-adoptively-transferred-cd8-t-cells-in-vivo
#18
Aude G Chapuis, Cindy Desmarais, Ryan Emerson, Thomas M Schmitt, Kendall Shibuya, Ivy Lai, Felecia Wagener, Jeffrey Chou, Ilana M Roberts, David G Coffey, Edus Warren, Harlan Robbins, Philip D Greenberg, Cassian Yee
Adoptively transferred tumor-specific cells can mediate tumor regression in cancers refractory to conventional therapy. Autologous polyclonal tumor-specific cytotoxic T cells (CTL) generated from peripheral blood and infused into patients with metastatic melanoma show enhanced persistence, compared to equivalent numbers of more extensively expanded monoclonal CTL, and are associated with complete remissions (CR) in select patients. We applied high-throughput T cell receptor Vβ sequencing (HTTCS) to identify individual clonotypes within CTL products, track them in vivo post-infusion and then deduce the pre-adoptive transfer (endogenous) frequencies of cells ultimately responsible for tumor regression...
February 2017: Science Immunology
https://www.readbyqxmd.com/read/28364502/altered-cd8-t-cell-lymphocyte-function-and-tc1-cell-stemness-contribute-to-enhanced-malignant-tumor-properties-in-murine-models-of-sleep-apnea
#19
Mahzad Akbarpour, Abdelnaby Khalyfa, Zhuanghong Qiao, Alex Gileles-Hillel, Isaac Almendros, Ramon Farré, David Gozal
Study Objective: The presence of obstructive sleep apnea (OSA) in patients with cancer appears to be accompanied by poorer outcomes. However, the mechanisms underlying such association are unknown. Tumor infiltrating lymphocytes (TILs), including CD8+ T cells, function as cytotoxic T lymphocytes (CTLs) and mount immune responses to cancer by the release of cytolytic enzymes, including granzyme B (GzmB), perforin (Prf), and cytokines such as interferon (IFN)-γ. Methods: Using established in vivo mouse models, we investigated CD8+ T cells and cancer stem cells (CSCs) in intermittent hypoxia (IH) and sleep fragmentation (SF) in the context of tumor environment...
February 1, 2017: Sleep
https://www.readbyqxmd.com/read/28359782/in-vivo-il-4-prevents-allo-antigen-driven-cd8-ctl-development
#20
Charles S Via, Kateryna Soloviova, Maksym Puliaiev, Roman Puliav, Irina Puliaeva, Suzanne C Morris, Fred D Finkelman
IL-4 has been shown to suppress acute graft vs. host disease (GVHD) in irradiated hosts. Here we evaluated whether IL-4 suppresses acute GVHD in the un-irradiated parent-into-F1 GVHD model with relevance to renal allograft rejection. IL-4 completely suppressed CD8 CTL when administered with donor cells however this effect was lost if its administration was delayed 3days. IL-4 did not inhibit donor CD8(+) T cell homing to the host spleen but rather prevented donor CD8(+) T cell differentiation into CTLs. Studies with IL-4Rα-deficient donor cells or recipient mice demonstrated that IL-4 effects on the host, rather than, or in addition to IL-4 effects on donor cells, were critical for suppression of CTL...
March 27, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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