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https://www.readbyqxmd.com/read/28323897/hcv-coinfection-contributes-to-hiv-pathogenesis-by-increasing-immune-exhaustion-in-cd8-t-cells
#1
Norma Rallón, Marcial García, Javier García-Samaniego, Noelia Rodríguez, Alfonso Cabello, Clara Restrepo, Beatriz Álvarez, Rosa García, Miguel Górgolas, José M Benito
BACKGROUND: There are several contributors to HIV-pathogenesis or insufficient control of the infection. However, whether HIV/HCV-coinfected population exhibits worst evolution of HIV-pathogenesis remains unclear. Recently, some markers of immune exhaustion have been proposed as preferentially upregulated on T-cells during HIV-infection. Herein, we have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection. PATIENTS AND METHODS: Ninety-six patients with chronic HIV-infection (60 HIV-monoinfected and 36 HIV/HCV-coinfected), and 20 healthy controls were included in the study...
2017: PloS One
https://www.readbyqxmd.com/read/28320090/treatment-with-anti-programmed-cell-death-1-pd-1-antibody-restored-postoperative-cd8-t-cell-dysfunction-by-surgical-stress
#2
Zhirong Sun, Anrong Mao, Yun Wang, Yanjun Zhao, Jiawei Chen, Pingbo Xu, Changhong Miao
Millions of patients benefit from surgery and are exposed to surgical stress. However, ample studies suggest that surgical stress contributes to tumor recurrence or distant metastases. Surgical stress suppresses CD8+ T cells (CTL) function which is vital for eliminating the malignant cells. Anti-programmed cell death 1 (PD-1) therapy is an effective and safe treatment that increases survival rate of patients with multiple cancers, however, whether anti-PD-1 therapy is able to reverse the immunosuppression following surgery remains largely unknown...
March 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319565/bone-marrow-graft-versus-host-disease-in-major-histocompatibility-complex-matched-murine-reduced-intensity-allogeneic-hemopoietic-cell-transplantation
#3
Kifah Shahin, Zamil Mattar, Pablo Silveira, Wei-Hsun Hsu, Linda Bendall, Derek Hart, Kenneth F Bradstock
BACKGROUND: Most clinical allogeneic hemopoietic cell transplants (alloHCT) are now performed using reduced intensity conditioning (RIC) instead of myeloablative (MAC) conditioning, however, the biology underlying this treatment remains incompletely understood. METHODS: We investigated a murine model of major histocompatibility complex (MHC)-matched multiple minor histocompatibility antigen mismatched alloHCT, using bone marrow (BM) cells and splenocytes from B6 (H-2) donor mice transplanted into BALB...
March 18, 2017: Transplantation
https://www.readbyqxmd.com/read/28319404/encapsulation-of-an-ep67-conjugated-ctl-peptide-vaccine-in-nanoscale-biodegradable-particles-increases-the-efficacy-of-respiratory-immunization-and-affects-the-magnitude-and-memory-subsets-of-vaccine-generated-mucosal-and-systemic-cd8-t-cells-in-a-diameter
#4
Bala Vamsi Krishna Karuturi, Shailendra B Tallapaka, Pravin Yeapuri, Stephen M Curran, Sam D Sanderson, Joseph A Vetro
The diameter of biodegradable particles used to co-encapsulate immunostimulants and subunit vaccines affects the magnitude of memory CD8(+) T cells generated by systemic immunization. Possible effects on the magnitude of CD8(+) T cells generated by mucosal immunization or memory subsets that potentially correlate more strongly with protection against certain pathogens, however, are unknown. In this study, we conjugated our novel host-derived mucosal immunostimulant, EP67, to the protective MCMV CTL epitope, pp89, through a lysosomal protease-labile double arginine linker (pp89-RR-EP67) and encapsulated in PLGA 50:50 micro- or nanoparticles...
March 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28319049/resisting-fatal-attraction-a-glioma-oncometabolite-prevents-cd8-t-cell-recruitment
#5
Liliana E Lucca, David A Hafler
Immunotherapy has emerged as a potent approach for treating aggressive cancers, such as non-small-cell lung tumors and metastatic melanoma. Clinical trials are now in progress for patients with malignant gliomas; however, a better understanding of how these tumors escape immune surveillance is required to enhance antitumor immune responses. With gliomas, the recruitment of CD8+ T cells to the tumor is impaired, in part preventing containment or elimination of the tumor. In this issue of the JCI, Kohanbash and colleagues present an elegant dissection of how gliomas exploit an enzymatic activity acquired through a common mutation to abrogate the migration of CD8+ T cells to the tumor...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28319047/isocitrate-dehydrogenase-mutations-suppress-stat1-and-cd8-t-cell-accumulation-in-gliomas
#6
Gary Kohanbash, Diego A Carrera, Shruti Shrivastav, Brian J Ahn, Naznin Jahan, Tali Mazor, Zinal S Chheda, Kira M Downey, Payal B Watchmaker, Casey Beppler, Rolf Warta, Nduka A Amankulor, Christel Herold-Mende, Joseph F Costello, Hideho Okada
Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG). LGG-associated IDH mutations confer gain-of-function activity by converting α-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG). Clinical samples and gene expression data from The Cancer Genome Atlas (TCGA) demonstrate reduced expression of cytotoxic T lymphocyte-associated genes and IFN-γ-inducible chemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318800/autoimmune-disease-development-based-on-possible-mislocalization-of-intracellular-and-extracellular-proteins
#7
Borros Arneth
BACKGROUND: T helper cells can differentiate into several subsets of T lymphocytes, including Th1, Th2, and regulatory T (Treg) cells. As a result of this ability to differentiate, the corresponding T cell receptor (TCR) spectra display considerable cellular plasticity and interchangeability. In contrast, T lymphocyte differentiation and separation into CD4(+) and/or CD8(+) T cell lines creates stable populations over a person's lifetime, which abrogates the plasticity and interchange between these cell types and their corresponding TCR spectra but results in considerable stability regarding the corresponding TCR sequences and spectra...
February 27, 2017: Immunobiology
https://www.readbyqxmd.com/read/28318765/in-vivo-electroporation-in-dna-vlp-prime-boost-preferentially-enhances-hiv-1-envelope-specific-igg2a-neutralizing-antibody-and-cd8-t-cell-responses
#8
Xun Huang, Qianqian Zhu, Xiaoxing Huang, Lifei Yang, Yufeng Song, Ping Zhu, Paul Zhou
Although in vivo electroporation (EP) has been utilized to improve immunogenicity in DNA vaccines alone or in prime-boost regimens with both proteins and viral-vectors, no studies on in vivo EP in DNA-VLP prime-boost regimens against HIV-1 have been reported. Previously we developed stably transfected Drosophila S2 clones to produce HIV-1 virus-like particles (VLP) and demonstrated that priming mice twice with DNA plasmids encoding HIV-1 gp120 and gag and boosting twice with HIV-1 VLP (i.e. DDVV immunization) elicited both envelope-specific antibody and envelope and gag-specific CD8 T cell responses...
March 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28317931/recruitment-of-bone-marrow-cd11b-gr-1-cells-by-polymeric-nanoparticles-for-antigen-cross-presentation
#9
Ya-Wun Yang, Wen-Hui Luo
The objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8(+) T cell responses via the CD11b(+)Gr(-)1(+) myeloid subpopulations in murine bone marrow (BM). PLGA NPs containing ovalbumin (OVA) were fabricated by the double-emulsion method. The CD11b(+)Gr-1(low)Ly-6C(high) and CD11b(+)Gr-1(high)Ly-6C(low) subsets from mice bone marrow were sorted and treated with the PLGA/OVA NPs, followed by co-culture with the carboxyfluorescein succinimidyl ester (CFSE)-labelled OT-I CD8(+) cells...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317872/preclinical-evaluation-of-the-efficacy-pharmacokinetics-and-immunogenicity-of-js-001-a-programmed-cell-death-protein-1-pd-1-monoclonal-antibody
#10
Jie Fu, Fang Wang, Li-Hou Dong, Jing Zhang, Cheng-Lian Deng, Xue-Li Wang, Xin-Yao Xie, Jing Zhang, Ruo-Xian Deng, Li-Bo Zhang, Hai Wu, Hui Feng, Bo Chen, Hai-Feng Song
JS-001 is the first monoclonal antibody (mAb) against programmed cell death protein-1 (PD-1) approved by the China Food and Drug Administration (CFDA) into the clinical trails. To date, however, no pre-clinical pharmacological and pharmacokinetic (PK) data are available. In this study, we investigated the efficacy of JS-001 and conducted a preclinical PK study, including the monitoring of anti-drug antibodies (ADAs). We found that JS-001 specifically bound to PD-1 antigen with an EC50 of 21 nmol/L, and competently blocked the binding of PD-1 antigen to PD-L1 and PD-L2 with IC50 of 3...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28317291/intravascular-t-cell-lymphoma-a-rare-poorly-characterized-entity-with-cytotoxic-phenotype
#11
Tara L Sharma, Gabrielle A Yeaney, Payam Soltanzadeh, Yuebing Li, Claudiu V Cotta
Intravascular T-cell lymphomas are rare, poorly characterized lesions. We discuss the clinical, radiologic and especially the laboratory characteristics of a lesion which presented in a 62-year-old woman with a history of progressive CNS abnormalities. Throughout the course of the disease, radiologic findings consisted mainly of multifocal mixed areas of ischemia and vasogenic edema involving cortical and subcortical regions. A brain biopsy identified an abnormal T-cell population confined to lumens of vessels...
March 20, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28315920/-unknown-title
#12
J S Schwartz, S Al-Mot, M F Endam, S Al-Romaih, J Madrenas, M Desrosiers
BACKGROUND: Staphylococcus aureus is a frequently implicated pathogen in chronic rhinosinusitis (CRS). S. aureus may promote commensalism by downregulating pro-inflammatory T cell host responses via an IL-10 mediated pathway. This finding, coupled with the observation that S. aureus and CD8+ T cell numbers are inversely correlated in CRS mucosa, suggests that S. aureus may evade immune destruction via IL-10 induction. To support this hypothesis, we evaluated i) whether IL-10 levels differ in CRS compared to controls (CTL) using microarray and immunohistochemistry and ii) whether IL-10 levels correlate with S...
March 19, 2017: Rhinology
https://www.readbyqxmd.com/read/28315060/results-of-a-phase-ib-trial-of-combination-immunotherapy-with-a-cd8-%C3%A2-t-cell-eliciting-vaccine-and-trastuzumab-in-breast-cancer-patients
#13
G Travis Clifton, Jennifer K Litton, Karen Arrington, Sathibalan Ponniah, Nuhad K Ibrahim, Victor Gall, Gheath Alatrash, George E Peoples, Elizabeth A Mittendorf
BACKGROUND: CD8+ T cell-eliciting vaccines are being investigated in breast cancer patients. Preclinical data showed that trastuzumab increases the susceptibility of tumor cells to lysis by vaccine-generated CD8+ T cells, suggesting potential benefit of a combination immunotherapy strategy. The current trial was undertaken to demonstrate the safety of this approach. METHODS: This study was designed as a dose-escalation trial enrolling clinically disease-free, human leukocyte antigen A2+ or A3+ , human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients...
March 17, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28314856/ubc9-is-required-for-positive-selection-and-late-stage-maturation-of-thymocytes
#14
Aibo Wang, Xiao Ding, Maud Demarque, Xindong Liu, Deng Pan, Huawei Xin, Bo Zhong, Xiaohu Wang, Anne Dejean, Wei Jin, Chen Dong
SUMOylation is an important posttranslational modification that regulates protein function in diverse biological processes. However, its role in early T cell development has not been genetically studied. UBC9 is the only E2 enzyme for all SUMOylation. In this study, by selectively deleting Ubc9 gene in T cells, we have investigated the functional roles of SUMOylation in T cell development. Loss of Ubc9 results in a significant reduction of CD4 and CD8 single-positive lymphocytes in both thymus and periphery...
March 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28314785/tumor-localized-secretion-of-soluble-pd1-enhances-oncolytic-virotherapy
#15
Mee Y Bartee, Katherine M Dunlap, Eric Bartee
Oncolytic virotherapy represents an attractive option for the treatment of a variety of aggressive or refractory tumors. While this therapy is effective at rapidly debulking directly injected tumor masses, achieving complete eradication of established disease has proven difficult. One method to overcome this challenge is to use oncolytic viruses to induce secondary anti-tumor immune responses. Unfortunately, while the initial induction of these immune responses is typically robust, their subsequent efficacy is often inhibited through a variety of immunoregulatory mechanisms, including the PD1/PDL1 T-cell checkpoint pathway...
March 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28314692/identification-of-an-atypical-etiological-head-and-neck-squamous-carcinoma-subtype-featuring-the-cpg-island-methylator-phenotype
#16
K Brennan, J L Koenig, A J Gentles, J B Sunwoo, O Gevaert
Head and neck squamous cell carcinoma (HNSCC) is broadly classified into HNSCC associated with human papilloma virus (HPV) infection, and HPV negative HNSCC, which is typically smoking-related. A subset of HPV negative HNSCCs occur in patients without smoking history, however, and these etiologically 'atypical' HNSCCs disproportionately occur in the oral cavity, and in female patients, suggesting a distinct etiology. To investigate the determinants of clinical and molecular heterogeneity, we performed unsupervised clustering to classify 528 HNSCC patients from The Cancer Genome Atlas (TCGA) into putative intrinsic subtypes based on their profiles of epigenetically (DNA methylation) deregulated genes...
March 1, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28314561/dna-vaccine-encoding-middle-east-respiratory-syndrome-coronavirus-s1-protein-induces-protective-immune-responses-in-mice
#17
Hang Chi, Xuexing Zheng, Xiwen Wang, Chong Wang, Hualei Wang, Weiwei Gai, Stanley Perlman, Songtao Yang, Jincun Zhao, Xianzhu Xia
The Middle East respiratory syndrome coronavirus (MERS-CoV), is an emerging pathogen that continues to cause outbreaks in the Arabian peninsula and in travelers from this region, raising the concern that a global pandemic could occur. Here, we show that a DNA vaccine encoding the first 725 amino acids (S1) of MERS-CoV spike (S) protein induces antigen-specific humoral and cellular immune responses in mice. With three immunizations, high titers of neutralizing antibodies (up to 1: 10(4)) were generated without adjuvant...
March 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28314222/radiation-induced-decrease-of-cd8-dendritic-cells-contributes-to-th1-th2-shift
#18
Hu Liu, Bailong Li, Xiaojing Jia, Yan Ma, Yifeng Gu, Pei Zhang, Qun Wei, Jianming Cai, Jianguo Cui, Fu Gao, Yanyong Yang
Exposure to ionizing radiation (IR) often reduce the helper T (Th) 1 like function, resulting in a Th1/Th2 imbalance, which could affect the efficacy of cancer radiotherapy. As the most potent antigen presenting cells, dendritic cells (DC) can be divided into several subsets with specialized function. However, there is no literature covering the changes of DC subsets and their roles in immune regulation in response to IR. In the present study, we were aimed to investigate the changes of DC subsets after IR and its relationship with Th1/Th2 immunity...
March 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28314212/gene-delivery-of-tipe2-inhibits-breast-cancer-development-and-metastasis-via-cd8-t-and-nk-cell-mediated-antitumor-responses
#19
Zhenhua Zhang, Li Liu, Shousong Cao, Yizhun Zhu, Qibing Mei
Breast cancer is the second leading cause of cancer-related deaths in the female patients which was mainly caused by metastasis. Development of target gene therapy for breast cancer to suppress tumor progress and metastasis will improve the therapeutic options and be of great benefit to the patients. Tumor necrosis factor-alpha-induced protein 8-like 2 is a novel molecule for maintaining immune homeostasis and is involved in cancer development. In the present study, we overexpressed TIPE2 in breast cancer cells to investigate the role of TIPE2 in the development of breast cancer...
March 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28306177/frequency-and-functional-characterization-of-exhausted-cd8-t-cells-in-chronic-lymphocytic-leukemia
#20
Saeid Taghiloo, Esmaeil Allahmoradi, Mohsen Tehrani, Hadi Hossein-Nataj, Ramin Shekarriz, Ghasem Janbabaei, Saeid Abediankenari, Hossein Asgarian-Omran
OBJECTIVES: The phenotypic and functional properties of Tim-3+/PD-1+/CD8+ cells as exhausted T-cells were investigated in chronic lymphocytic leukemia (CLL). METHODS: Frequency of CD8+/Tim-3+/PD-1+ exhausted cells was determined by flow cytometry. For functional analysis, magnetic beads isolated CD8+ T-cells were stimulated with PHA and PMA/ionocymin to assess their proliferative responses and cytokine production by MTT and ELISA, respectively. Cytotoxic activity of isolated CD8+ T-cells was determined using CD107a degranulation assay...
March 17, 2017: European Journal of Haematology
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