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https://www.readbyqxmd.com/read/28213500/inducible-t-cell-kinase-regulates-the-acquisition-of-cytolytic-capacity-and-degranulation-in-cd8-ctls
#1
Senta M Kapnick, Jane C Stinchcombe, Gillian M Griffiths, Pamela L Schwartzberg
Patients with mutations in inducible T cell kinase (ITK) are susceptible to viral infections, particularly EBV, suggesting that these patients have defective function of CD8(+) CTLs. In this study, we evaluated the effects of ITK deficiency on cytolysis in murine CTLs deficient in ITK, and both human and murine cells treated with an ITK inhibitor. We find that ITK deficiency leads to a global defect in the cytolysis of multiple targets. The absence of ITK both affected CTL expansion and delayed the expression of cytolytic effectors during activation...
February 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28210631/immunogenicity-and-cross-protection-in-mice-afforded-by-pandemic-h1n1-live-attenuated-influenza-vaccine-containing-wild-type-nucleoprotein
#2
Andrey Rekstin, Irina Isakova-Sivak, Galina Petukhova, Daniil Korenkov, Igor Losev, Tatiana Smolonogina, Tatiana Tretiak, Svetlana Donina, Svetlana Shcherbik, Tatiana Bousse, Larisa Rudenko
Since conserved viral proteins of influenza virus, such as nucleoprotein (NP) and matrix 1 protein, are the main targets for virus-specific CD8+ cytotoxic T-lymphocytes (CTLs), we hypothesized that introduction of the NP gene of wild-type virus into the genome of vaccine reassortants could lead to better immunogenicity and afford better protection. This paper describes in vitro and in vivo preclinical studies of two new reassortants of pandemic H1N1 live attenuated influenza vaccine (LAIV) candidates. One had the hemagglutinin (HA) and neuraminidase (NA) genes from A/South Africa/3626/2013 H1N1 wild-type virus on the A/Leningrad/134/17/57 master donor virus backbone (6 : 2 formulation) while the second had the HA, NA, and NP genes of the wild-type virus on the same backbone (5 : 3 formulation)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28197365/crispr-cas9-mediated-disruption-of-pd-1-on-human-t-cells-for-adoptive-cellular-therapies-of-ebv-positive-gastric-cancer
#3
Shu Su, Zhengyun Zou, Fangjun Chen, Naiqing Ding, Juan Du, Jie Shao, Lin Li, Yao Fu, Bian Hu, Yang Yang, Huizi Sha, Fanyan Meng, Jia Wei, Xingxu Huang, Baorui Liu
The successful use of immune cell checkpoint inhibitors PD-1 and PD-L1, over the past 5 y has raised the concern of using immunotherapy to treat various cancers. Epstein-Barr virus-associated gastric cancer (EBVaGC) exhibits high infiltration of lymphocytes and high amplification of immune-related genes including PD-L1 as distinguished from Epstein-Barr virus-non-associated gastric cancer (EBVnGC). Here, we presume that this PD-1/PD-L1 pathway may hinder the efficacy of adoptive T cell therapy toward EBVaGC...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196594/inactivation-of-interferon-receptor-promotes-the-establishment-of-immune-privileged-tumor-microenvironment
#4
Kanstantsin V Katlinski, Jun Gui, Yuliya V Katlinskaya, Angelíca Ortiz, Riddhita Chakraborty, Sabyasachi Bhattacharya, Christopher J Carbone, Daniel P Beiting, Melanie A Girondo, Amy R Peck, Ellen Puré, Priya Chatterji, Anil K Rustgi, J Alan Diehl, Constantinos Koumenis, Hallgeir Rui, Serge Y Fuchs
Refractoriness of solid tumors, including colorectal cancers (CRCs), to immunotherapies is attributed to the immunosuppressive tumor microenvironment that protects malignant cells from cytotoxic T lymphocytes (CTLs). We found that downregulation of the type I interferon receptor chain IFNAR1 occurs in human CRC and mouse models of CRC. Downregulation of IFNAR1 in tumor stroma stimulated CRC development and growth, played a key role in formation of the immune-privileged niche, and predicted poor prognosis in human CRC patients...
February 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28192149/serum-uric-acid-and-anti-n-methyl-d-aspartate-receptor-encephalitis
#5
Yaqing Shu, Yuge Wang, Tingting Lu, Rui Li, Xiaobo Sun, Jing Li, Yanyu Chang, Xueqiang Hu, Zhengqi Lu, Wei Qiu
BACKGROUND: Uric acid (UA) levels are associated with autoimmune and neurodegenerative disorders, but their relationship with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is unknown. METHODS: UA levels were evaluated in 58 patients with anti-NMDAR encephalitis, and 58 age- and sex-matched healthy controls (CTLs). Follow-up evaluations of 30 out of the 58 patients with anti-NMDAR encephalitis were conducted 3 months after admission. Modified Rankin scale (mRS) scores and clinical and cerebrospinal fluid parameters were evaluated in all anti-NMDAR encephalitis patients...
February 9, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28188673/socs-potential-immune-checkpoint-molecules-for-cancer-immunotherapy
#6
REVIEW
Shunsuke Chikuma, Mitsuhiro Kanamori, Setsuko Mise-Omata, Akihiko Yoshimura
Inhibition of immune checkpoint molecules, PD-1 and CTLA4, has been shown to be a promising cancer treatment. PD-1 and CTLA4 inhibit TCR and co-stimulatory signals, respectively. The third T cell activation signal represents the signals from the cytokine receptors. The cytokine Interferon-γ (IFNγ) plays an important role in anti-tumor immunity by activating cytotoxic T cells (CTLs). Most cytokines use the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, and the suppressors of cytokine signaling (SOCS) family of proteins are major negative regulators of the JAK/STAT pathway...
February 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28179527/hiv-specific-granzyme-b-but-not-interferon-%C3%AE-secreting-t-cells-are-associated-with-reduced-viral-reservoirs-in-early-hiv-infection
#7
Feng Yun Yue, Jared C Cohen, Mu Ho, A K M Nur-Ur Rahman, Jun Liu, Shariq Mujib, Aamir Saiyed, Sabrina Hundal, Alexandra Khozin, Phil Bonner, Daheng Liu, Erika Benko, Colin Kovacs, Mario Ostrowski
A major barrier to an Human Immunodeficiency Virus Type 1 (HIV) infection cure is the establishment of a viral reservoir despite cART. It is unclear how HIV-specific CTLs influence the size of the reservoir in early HIV infection. 28 subjects with early HIV infection were recruited to receive cART and followed for 48 weeks. HIV reservoirs in peripheral CD4+ T cells measured by cell associated proviral DNA and viral outgrowth cultures were determined at baseline and 48 weeks of cART. At baseline, Granzyme B and IFN-γ ELISpot assays were performed with peptides spanning the HIV proteome...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28166682/clonally-expanded-cytotoxic-cd4-t-cells-and-the-pathogenesis-of-igg4-related-disease
#8
Hamid Mattoo, John H Stone, Shiv Pillai
IgG4-related disease (IgG4-RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions, with dense lymphoplasmacytic infiltrates containing a preponderance of IgG4-expressing plasma cells. CD4(+) T cells and B cells constitute the major inflammatory cell populations in IgG4-RD lesions. IgG4-RD patients with active, untreated disease show a marked expansion of plasmablasts in the circulation. Although the therapeutic depletion of B cells suggests a role for these cells in the disease, a direct role for B cells or IgG4 in the pathogenesis of IgG4-RD is yet to be demonstrated...
February 2017: Autoimmunity
https://www.readbyqxmd.com/read/28161330/testosterone-increases-ccl-2-expression-in-visceral-adipose-tissue-from-obese-women-of-reproductive-age
#9
Nicolás Crisosto, Cristián Flores, Manuel Maliqueo, Bárbara Echiburú, Jaime Vásquez, Fernando Maluenda, Teresa Sir-Petermann
CONTEXT: Hyperandrogenic states and obesity in women are associated with insulin-resistance. Androgens reduce glucose uptake in adipose cells and increase TNFα production in peripheral monocytes. Inflammatory cytokines have a known detrimental effect on insulin resistance. The aim of the present study was to explore the role of testosterone in local cytokine production in visceral adipose tissue from women of reproductive age. DESIGN: Twenty-four women 18-40 years old, undergoing elective abdominal surgery for benign and non-inflammatory conditions, were recruited for the study...
February 1, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28153727/cd40-agonist-converting-ctl-exhaustion-via-the-activation-of-the-mtorc1-pathway-enhances-pd-1-antagonist-action-in-rescuing-exhausted-ctls-in-chronic-infection
#10
Aizhang Xu, Rong Wang, Andrew Freywald, Kristoffor Stewart, Suresh Tikoo, Jianqing Xu, Changyu Zheng, Jim Xiang
Expansion of PD-1-expressing CD8(+) cytotoxic T lymphocytes (CTLs) and associated CTL exhaustion are chief issues for ineffective virus-elimination in chronic infectious diseases. PD-1 blockade using antagonistic anti-PD-L1 antibodies results in a moderate conversion of CTL exhaustion. We previously demonstrated that CD40L signaling of ovalbumin (OVA)-specific vaccine, OVA-Texo, converts CTL exhaustion via the activation of the mTORC1 pathway in OVA-expressing adenovirus (AdVova)-infected B6 mice showing CTL inflation and exhaustion...
January 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28139642/experimental-evidence-for-circular-inference-in-schizophrenia
#11
Renaud Jardri, Sandrine Duverne, Alexandra S Litvinova, Sophie Denève
Schizophrenia (SCZ) is a complex mental disorder that may result in some combination of hallucinations, delusions and disorganized thinking. Here SCZ patients and healthy controls (CTLs) report their level of confidence on a forced-choice task that manipulated the strength of sensory evidence and prior information. Neither group's responses can be explained by simple Bayesian inference. Rather, individual responses are best captured by a model with different degrees of circular inference. Circular inference refers to a corruption of sensory data by prior information and vice versa, leading us to 'see what we expect' (through descending loops), to 'expect what we see' (through ascending loops) or both...
January 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28131992/the-mll1-h3k4me3-axis-mediated-pd-l1-expression-and-pancreatic-cancer-immune-evasion
#12
Chunwan Lu, Amy V Paschall, Huidong Shi, Natasha Savage, Jennifer L Waller, Maria E Sabbatini, Nicholas H Oberlies, Cedric Pearce, Kebin Liu
BACKGROUND: Pancreatic cancer is one of the cancers where anti-PD-L1/PD-1 immunotherapy has been unsuccessful. What confers pancreatic cancer resistance to checkpoint immunotherapy is unknown. The aim of this study is to elucidate the underlying mechanism of PD-L1 expression regulation in the context of pancreatic cancer immune evasion. METHODS: Pancreatic cancer mouse models and human specimens were used to determine PD-L1 and PD-1 expression and cancer immune evasion...
January 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28127508/elevated-cerebrospinal-fluid-uric-acid-during-relapse-of-neuromyelitis-optica-spectrum-disorders
#13
Yaqing Shu, Haiyan Li, Lei Zhang, Yuge Wang, Youming Long, Rui Li, Wei Qiu, Zhengqi Lu, Xueqiang Hu, Fuhua Peng
INTRODUCTION: Previous studies have shown that serum uric acid (UA) modulates outcomes of neurological diseases, although little is known about cerebrospinal fluid (CSF) UA levels in neuromyelitis optica spectrum disorders (NMOSDs). METHODS: Cerebrospinal fluid and serum UA levels were measured in samples from 68 patients, including NMOSDs during relapse (n = 38) and controls with noninflammatory and non-neurodegenerative diseases (CTLs, n = 30). Correlation analysis was performed between CSF UA and clinical characteristics, serum UA, and blood-brain barrier integrity in NMOSDs...
January 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28118287/abnormal-functional-connectivity-of-the-amygdala-in-first-episode-and-untreated-adult-major-depressive-disorder-patients-with-different-ages-of-onset
#14
Jing Ye, Zonglin Shen, Xiufeng Xu, Shuran Yang, Wei Chen, Xiaoyan Liu, Yi Lu, Fang Liu, Jin Lu, Na Li, Xuejin Sun, Yuqi Cheng
Major depressive disorder (MDD) is a common mental disorder with high morbidity. As a part of the limbic system, the amygdala is important in the processing of emotional information. Structural and functional connectivity (FC) abnormalities in the amygdala have been observed in MDD patients. The present study was carried out to identify the features of amygdala FC in adult MDD patients with different ages of onset. Sixty-nine first-episode and untreated MDD patients and 81 healthy controls (CTLs) were included in this study and underwent 3D structural imaging and resting-state functional MRI scanning...
January 21, 2017: Neuroreport
https://www.readbyqxmd.com/read/28116322/genetically-modified-t-cell-based-adoptive-immunotherapy-in-hematological-malignancies
#15
REVIEW
Baixin Ye, Creed M Stary, Qingping Gao, Qiongyu Wang, Zhi Zeng, Zhihong Jian, Lijuan Gu, Xiaoxing Xiong
A significant proportion of hematological malignancies remain limited in treatment options. Immune system modulation serves as a promising therapeutic approach to eliminate malignant cells. Cytotoxic T lymphocytes (CTLs) play a central role in antitumor immunity; unfortunately, nonspecific approaches for targeted recognition of tumor cells by CTLs to mediate tumor immune evasion in hematological malignancies imply multiple mechanisms, which may or may not be clinically relevant. Recently, genetically modified T-cell-based adoptive immunotherapy approaches, including chimeric antigen receptor (CAR) T-cell therapy and engineered T-cell receptor (TCR) T-cell therapy, promise to overcome immune evasion by redirecting the specificity of CTLs to tumor cells...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28114424/cellular-immune-responses-for-squamous-cell-carcinoma-antigen-recognized-by-t-cells-3-in-patients-with-hepatocellular-carcinoma
#16
Kiichiro Kaji, Eishiro Mizukoshi, Tatsuya Yamashita, Kuniaki Arai, Hajime Sunagozaka, Kazumi Fushimi, Hidetoshi Nakagawa, Kazutoshi Yamada, Takeshi Terashima, Masaaki Kitahara, Shuichi Kaneko
BACKGROUND & AIMS: Squamous cell carcinoma antigen recognized by T cells 3 (SART3), a tumor-associated antigen expressed in many cancers, functions in tumor rejection. In this study, we investigated its usefulness as an immunotherapeutic target in hepatocellular carcinoma (HCC). METHODS: The expression of SART3 in hepatoma cell lines and HCC tissues was investigated by immunofluorescence and immunohistochemical analyses. Two peptides derived from SART3 (SART3109 and SART3315) were used for immunological analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28110220/hypoxia-inducing-factor-hif-1%C3%AE-derived-peptide-capable-of-inducing-cancer-reactive-cytotoxic-t-lymphocytes-from-hla-a24-patients-with-renal-cell-carcinoma
#17
Takafumi Minami, Naoki Matsumura, Koichi Sugimoto, Nobutaka Shimizu, Marco De Velasco, Masahiro Nozawa, Kazuhiro Yoshimura, Nanae Harashima, Mamoru Harada, Hirotsugu Uemura
Hypoxic tumor microenvironment makes cancer cells to be therapy-resistant and hypoxia-inducing factors (HIFs) play a central role in hypoxic adaptation. Especially, renal cell carcinoma (RCC) is often associated with von Hippel-Lindau (VHL) gene mutations, leading to up-regulation of HIFs. However, from a different point of view, this suggests the possibility that HIFs could be promising targets in anti-cancer therapy. In this study, we searched for HIF-1α-derived peptides that are able to induce RCC-reactive cytotoxic T lymphocytes (CTLs) from HLA-A24(+) RCC patients...
January 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28110170/tailoring-polymeric-hybrid-micelles-with-lymph-node-targeting-ability-to-improve-the-potency-of-cancer-vaccines
#18
Qin Zeng, Hanmei Li, Hao Jiang, Jiao Yu, Ying Wang, Huan Ke, Tao Gong, Zhirong Zhang, Xun Sun
It has been widely accepted that lymph nodes (LNs) are critical targets of cancer vaccines and particles sized between 10 and 100 nm with a neutral or negative surface charge are preferred for lymphatic transfer after subcutaneous or intradermal injection. However their limited uptake by antigen presenting cells (APCs) and inadequate retention within LNs undoubtedly restrains their strength on activating T cell immunity. Here, we address this issue by tailoring the physicochemical properties of polymeric hybrid micelles (HMs), which are self-assembled from two amphiphilic diblock copolymers, poly-(ethylene glycol) phosphorethanolamine (PEG-PE) and polyethylenimine-stearic acid conjugate (PSA) via hydrophobic and electrostatic interactions...
January 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28100962/ctls-2016-and-the-formation-of-a-pan-european-professional-society-through-the-lens-of-an-abrf-founding-member
#19
Ronald L Niece
No abstract text is available yet for this article.
January 5, 2017: Journal of Biomolecular Techniques: JBT
https://www.readbyqxmd.com/read/28100832/reporter-gene-imaging-of-targeted-t-cell-immunotherapy-in-recurrent-glioma
#20
Khun Visith Keu, Timothy H Witney, Shahriar Yaghoubi, Jarrett Rosenberg, Anita Kurien, Rachel Magnusson, John Williams, Frezghi Habte, Jamie R Wagner, Stephen Forman, Christine Brown, Martin Allen-Auerbach, Johannes Czernin, Winson Tang, Michael C Jensen, Behnam Badie, Sanjiv S Gambhir
High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8(+) cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[(18)F]fluoro-3-(hydroxymethyl)butyl]guanine ([(18)F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs...
January 18, 2017: Science Translational Medicine
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