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Cytotoxic T cell

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https://www.readbyqxmd.com/read/29444189/cross-priming-induces-immunodomination-in-the-presence-of-viral-mhc-class-i-inhibition
#1
Elvin J Lauron, Liping Yang, Jabari I Elliott, Maria D Gainey, Daved H Fremont, Wayne M Yokoyama
Viruses have evolved mechanisms of MHCI inhibition in order to evade recognition by cytotoxic CD8+ T cells (CTLs), which is well-illustrated by our prior studies on cowpox virus (CPXV) that encodes potent MHCI inhibitors. Deletion of CPXV viral MHCI inhibitors markedly attenuated in vivo infection due to effects on CTL effector function, not priming. However, the CTL response to CPXV in C57BL/6 mice is dominated by a single peptide antigen presented by H-2Kb. Here we evaluated the effect of viral MHCI inhibition on immunodominant (IDE) and subdominant epitopes (SDE) as this has not been thoroughly examined...
February 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29442287/recent-developments-in-adolescent-and-young-adult-aya-acute-lymphoblastic-leukemia
#2
REVIEW
Victor M Orellana-Noia, Michael G Douvas
PURPOSE OF REVIEW: Adolescent and Young Adult (AYA) Oncology is a relatively new field encompassing research in the unique pathophysiology, clinical care, and psychosocial issues facing patients between the ages of 15 and 40 with cancer. About 100,000 of the approximately 1.5 million people diagnosed annually with cancer in the USA are in this age range. This chapter will review notable new developments in the care of adolescents and young adults with acute lymphoblastic leukemia (ALL) within the last 3 years...
February 14, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29441979/using-pva-and-tpgs-as-combined-emulsifier-in-nanoprecipitation-method-improves-characteristics-and-anticancer-activity-of-ibuprofen-loaded-plga-nanoparticles
#3
A Sahin, F Spiroux, I Guedon, F B Arslan, E T Sarcan, T Ozkan, N Colak, S Yuksel, S Ozdemir, B Ozdemir, S Akbas, G Ultav, Y Aktas, Y Capan
In the preparation of nanoparticles (NPs) by the nanoprecipitation method, emulsifiers play a key role for NPs' characteristics. The present study aimed to investigate the combined emulsifier effect on ibuprofen loaded poly(lactic-co-glycolic acid) (PLGA) NPs' characteristics and anticancer activity. Ibuprofen loaded PLGA NPs were prepared by nanoprecipitation using different concentrations of PVA (poly(vinyl alcohol)) or PVA-TPGS (d-α-tocopherol polyethylene glycol 1000 succinate) combination as emulsifier...
September 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29441705/injectable-tough-alginate-cryogels-as-cancer-vaccines
#4
Ting-Yu Shih, Serena O Blacklow, Aileen W Li, Benjamin R Freedman, Sidi Bencherif, Sandeep T Koshy, Max C Darnell, David J Mooney
A covalently crosslinked methacrylated (MA)-alginate cryogel vaccine has been previously shown to generate a potent response against murine melanoma, but is not mechanically robust and requires a large 16G needle for delivery. Here, covalent and ionic crosslinking of cryogels are combined with the hypothesis that this will result in a tough MA-alginate cryogel with improved injectability. All tough cryogels can be injected through a smaller, 18G needle without sustaining any damage, while covalently crosslinked-only cryogels break after injection...
February 14, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29440406/chimeric-antigen-receptor-t-cells-form-nonclassical-and-potent-immune-synapses-driving-rapid-cytotoxicity
#5
A J Davenport, R S Cross, K A Watson, Y Liao, W Shi, H M Prince, P A Beavis, J A Trapani, M H Kershaw, D S Ritchie, P K Darcy, P J Neeson, M R Jenkins
Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters...
February 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29439708/possible-relationship-between-fibrosis-of-igg4-related-thymitis-and-the-profibrotic-cytokines-transforming-growth-factor-beta-1-interleukin-1-beta-and-interferon-gamma-a-case-report
#6
Atsuko Masunaga, Fumihiro Ishibashi, Eitetsu Koh, Takashi Oide, Yasuo Sekine, Kenzo Hiroshima
BACKGROUND: IgG4-related disease often forms a mass and the affected lesion is clinically removed because the mass cannot be differentiated from a neoplasm. Affected lesions commonly occur in the pancreas, hepatobiliary tract, kidney, and retroperitoneum. However, the lesion rarely occurs in the thymus. A histological worldwide consensus of IgG4-related disease proposed that pathological diagnosis of IgG4-related disease should meet more than two of three major features: 1) dense lymphoplasmacytic infiltration with greater than 40% IgG4+/IgG+ plasma cells, 2) storiform fibrosis; and 3) obliterative phlebitis...
January 17, 2018: Diagnostic Pathology
https://www.readbyqxmd.com/read/29439476/virus-like-vaccines-against-hiv
#7
REVIEW
Anne-Marie C Andersson, Melanie Schwerdtfeger, Peter J Holst
Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses. Here, we review the emerging concept of merging these two technologies into virus-like-vaccines (VLVs) for the targeting of HIV...
February 11, 2018: Vaccines
https://www.readbyqxmd.com/read/29438695/eradication-of-triple-negative-breast-cancer-cells-by-targeting-glycosylated-pd-l1
#8
Chia-Wei Li, Seung-Oe Lim, Ezra M Chung, Yong-Soo Kim, Andrew H Park, Jun Yao, Jong-Ho Cha, Weiya Xia, Li-Chuan Chan, Taewan Kim, Shih-Shin Chang, Heng-Huan Lee, Chao-Kai Chou, Yen-Liang Liu, Hsin-Chih Yeh, Evan P Perillo, Andrew K Dunn, Chu-Wei Kuo, Kay-Hooi Khoo, Jennifer L Hsu, Yun Wu, Jung-Mao Hsu, Hirohito Yamaguchi, Tzu-Hsuan Huang, Aysegul A Sahin, Gabriel N Hortobagyi, Stephen S Yoo, Mien-Chie Hung
Protein glycosylation provides proteomic diversity in regulating protein localization, stability, and activity; it remains largely unknown whether the sugar moiety contributes to immunosuppression. In the study of immune receptor glycosylation, we showed that EGF induces programmed death ligand 1 (PD-L1) and receptor programmed cell death protein 1 (PD-1) interaction, requiring β-1,3-N-acetylglucosaminyl transferase (B3GNT3) expression in triple-negative breast cancer. Downregulation of B3GNT3 enhances cytotoxic T cell-mediated anti-tumor immunity...
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29438386/doxycycline-inhibits-experimental-cerebral-malaria-by-reducing-inflammatory-immune-reactions-and-tissue-degrading-mediators
#9
Kim E Schmidt, Janina M Kuepper, Beatrix Schumak, Judith Alferink, Andrea Hofmann, Shanshan W Howland, Laurent Rénia, Andreas Limmer, Sabine Specht, Achim Hoerauf
Malaria ranks among the most important infectious diseases worldwide and affects mostly people living in tropical countries. Mechanisms involved in disease progression are still not fully understood and specific treatments that might interfere with cerebral malaria (CM) are limited. Here we show that administration of doxycycline (DOX) prevented experimental CM (ECM) in Plasmodium berghei ANKA (PbA)-infected C57BL/6 wildtype (WT) mice in an IL-10-independent manner. DOX-treated mice showed an intact blood-brain barrier (BBB) and attenuated brain inflammation...
2018: PloS One
https://www.readbyqxmd.com/read/29438058/assessment-of-antibody-dependent-cellular-cytotoxicity-by-flow-cytometry
#10
Thomas D Duensing, Susan R Watson
A useful feature of therapeutic antibodies is the ability to kill the cells to which they bind. Antibodies are capable of mediating cell killing in a variety of ways. Apoptosis, complement-mediated mechanisms, and antibody-dependent cellular cytotoxicity (ADCC) are all effects that can be assayed to characterize lead antibody candidates. Extensive, multidose characterizations of a series of candidates can be performed in a short amount of time using assays developed for high-throughput flow cytometry systems...
February 1, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29437954/t-cell-receptors-for-the-hiv-kk10-epitope-from-patients-with-differential-immunologic-control-are-functionally-indistinguishable
#11
Alok V Joglekar, Zhe Liu, Jeffrey K Weber, Yong Ouyang, John D Jeppson, Won Jun Noh, Pedro A Lamothe-Molina, Huabiao Chen, Seung-Gu Kang, Michael T Bethune, Ruhong Zhou, Bruce D Walker, David Baltimore
HIV controllers (HCs) are individuals who can naturally control HIV infection, partially due to potent HIV-specific CD8+ T cell responses. Here, we examined the hypothesis that superior function of CD8+ T cells from HCs is encoded by their T cell receptors (TCRs). We compared the functional properties of immunodominant HIV-specific TCRs obtained from HLA-B*2705 HCs and chronic progressors (CPs) following expression in primary T cells. T cells transduced with TCRs from HCs and CPs showed equivalent induction of epitope-specific cytotoxicity, cytokine secretion, and antigen-binding properties...
February 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29437871/gut-microbiota-modulate-t-cell-trafficking-into-human-colorectal-cancer
#12
Eleonora Cremonesi, Valeria Governa, Jesus Francisco Glaus Garzon, Valentina Mele, Francesca Amicarella, Manuele Giuseppe Muraro, Emanuele Trella, Virginie Galati-Fournier, Daniel Oertli, Silvio Raffael Däster, Raoul A Droeser, Benjamin Weixler, Martin Bolli, Raffaele Rosso, Ulrich Nitsche, Nina Khanna, Adrian Egli, Simone Keck, Julia Slotta-Huspenina, Luigi M Terracciano, Paul Zajac, Giulio Cesare Spagnoli, Serenella Eppenberger-Castori, Klaus-Peter Janssen, Lubor Borsig, Giandomenica Iezzi
OBJECTIVE: Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. DESIGN: Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues...
February 6, 2018: Gut
https://www.readbyqxmd.com/read/29437789/targeted-bite-expression-by-an-oncolytic-vector-augments-therapeutic-efficacy-against-solid-tumors
#13
Tobias Speck, Johannes Pw Heidbuechel, Rūta Veinalde, Dirk Jaeger, Christof von Kalle, Claudia R Ball, Guy Ungerechts, Christine E Engeland
PURPOSE: Immunotherapy with bispecific T cell engagers has achieved striking success against hematological malignancies, but efficacy against solid tumors has been limited. We hypothesized that oncolytic measles viruses encoding bispecific T cell engagers (MV-BiTEs) represent a safe and effective treatment against solid tumors through local BiTE expression, direct tumor cell lysis and in situ tumor vaccination. EXPERIMENTAL DESIGN: To test this hypothesis, we generated MV-BiTEs from the Edmonston B vaccine strain to target two model antigens...
February 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29437277/identification-of-native-and-post-translationally-modified-hla-b-57-01-restricted-hiv-envelope-derived-epitopes-using-immunoproteomics
#14
Sri H Ramarathinam, Stephanie Gras, Sheilajen Alcantara, Amanda W S Yeung, Nicole A Mifsud, Secondo Sonza, Patricia T Illing, Elias N Glaros, Robert J Center, Shane Thomas, Stephen J Kent, Nicola Ternette, Damian F J Purcell, Jamie Rossjohn, Anthony W Purcell
The recognition of pathogen-derived peptides by T lymphocytes is the cornerstone of adaptive immunity, whereby intracellular antigens are degraded in the cytosol and short peptides assemble with class I human leukocyte antigen (HLA) molecules in the endoplasmic reticulum (ER). These peptide-HLA complexes egress to the cell surface and are scrutinized by cytotoxic CD8+ T-cells leading to the eradication of the infected cell. Here we identify naturally presented HLA-B*57:01 bound peptides derived from the envelope protein of the human immunodeficiency virus (HIVenv)...
February 13, 2018: Proteomics
https://www.readbyqxmd.com/read/29436180/sweet-vector-for-gene-delivery-the-sugar-decoration-of-polyplexes-reduces-cytotoxicity-with-a-balanced-effect-on-gene-expression
#15
Lindomar J C Albuquerque, Alex C Alavarse, Maria C Carlan da Silva, Morgana S Zilse, Maitê T Barth, Ismael C Bellettini, Fernando C Giacomelli
The use of sugar-functionalized polyplexes as a nonviral gene delivery vector with lower cytotoxicity than the well-known polymeric carrier branched polyethyleneimine (BPEI) is investigated. The substitution of primary amine groups in the BPEI chains with lactose residues leads to larger polyplexes, presumably due to the higher amount of polymer required to complete DNA condensation. Nevertheless, the sugar functionalization substantially reduces the cytotoxicity of the assemblies. The nanocomplexes are taken up by the cells to a greater extent, whereas the levels of gene expression are maintained compared to those obtained using BPEI, which is known for its excellent transfection efficiency...
February 2018: Macromolecular Bioscience
https://www.readbyqxmd.com/read/29435173/crispr-knock-out-of-programmed-cell-death-protein-1-enhances-anti-tumor-activity-of-cytotoxic-t-lymphocytes
#16
Zhilong Zhao, Long Shi, Wei Zhang, Jinsheng Han, Shaohui Zhang, Zexian Fu, Jianhui Cai
Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that functions to attenuate T cell activation. In this study, we knocked out (KO) PD-1 in cytotoxic T lymphocytes (CTLs) using CRISPR-Cas9 system to evaluate its effect on the anti-tumor activity of the CTLs against multiple myeloma (MM). Results show that PD-1 KO CTLs facilitate apoptosis and caspase activation of the co-cultured MM cells and enhanced MM cell death by 36% compared with the control. PD-1 KO also increased TNF-α and IFN-γ secretion of the CTLs by 2...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435156/cis-trimethoxy-resveratrol-induces-intrinsic-apoptosis-via-prometaphase-arrest-and-prolonged-cdk1-activation-pathway-in-human-jurkat-t-cells
#17
Chae Eun Kim, Do Youn Jun, Jong-Sik Kim, Young Ho Kim
Cis-trimethoxy resveratrol (cis-3M-RES) induced dose-dependent cytotoxicity and apoptotic DNA fragmentation in Jurkat T cell clones (JT/Neo); however, it induced only cytostasis in BCL-2-overexpressing cells (JT/BCL-2). Treatment with 0.25 μM cis-3M-RES induced G2/M arrest, BAK activation, Δψm loss, caspase-9 and caspase-3 activation, and poly (ADP-ribose) polymerase (PARP) cleavage in JT/Neo cells time-dependently but did not induce these events, except G2/M arrest, in JT/BCL-2 cells. Moreover, cis-3M-RES induced CDK1 activation, BCL-2 phosphorylation at Ser-70, MCL-1 phosphorylation at Ser-159/Thr-163, and BIM (BIMEL and BIML) phosphorylation irrespective of BCL-2 overexpression...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435138/personalized-adoptive-immunotherapy-for-patients-with-ebv-associated-tumors-and-complications-evaluation-of-novel-naturally-processed-and-presented-ebv-derived-t-cell-epitopes
#18
Maren Bieling, Sabine Tischer, Ulrich Kalinke, Rainer Blasczyk, Søren Buus, Britta Maecker-Kolhoff, Britta Eiz-Vesper
Morbidity and mortality of immunocompromised patients are increased by primary infection with or reactivation of Epstein-Barr virus (EBV), possibly triggering EBV+ post-transplant lymphoproliferative disease (PTLD). Adoptive transfer of EBV-specific cytotoxic T cells (EBV-CTLs) promises a non-toxic immunotherapy to effectively prevent or treat these complications. To improve immunotherapy and immunomonitoring this study aimed at identifying and evaluating naturally processed and presented HLA-A*03:01-restricted EBV-CTL epitopes as immunodominant targets...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435066/potential-anticancer-effect-of-prostratin-through-sik3-inhibition
#19
Dalal Alotaibi, Suneetha Amara, Terrance L Johnson, Venkataswarup Tiriveedhi
Prostratin, a phorbol ester natural plant compound, has been demonstrated to exert an anti-retroviral effect through activation of latent cluster of differentiation (CD)4+T lymphocytes and inhibition of viral entry into the cell through downregulation of chemokine receptor type 4 (CXCR4) expression. However, the potential effect of prostratin on cancer is yet to be defined. As CXCR4 is well known to induce cancer migration, it was hypothesized that prostratin induces an anti-cancer effect through inhibition of CXCR4 expression...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29435021/long-lasting-memory-of-cellular-immunity-in-a-chronic-myeloid-leukemia-patient-maintains-molecular-response-5-after-cessation-of-dasatinib
#20
Tatsuro Jo, Kazuhiro Noguchi, Shizuka Hayashi, Sadaharu Irie, Risa Hayase, Haruna Shioya, Youhei Kaneko, Kensuke Horio, Jun Taguchi
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib are primarily used in the initial treatment of chronic phase (CP)-chronic myeloid leukemia (CML), as CMLs harbor the BCR-ABL fusion product. An increased number of lymphocytes and large granular lymphocytes (LGLs) have been observed in patients treated with dasatinib, but not other TKIs. The LGLs have been reported to be primarily natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). In the present study, a CP-CML patient who has maintained molecular response 5 for >2...
March 2018: Oncology Letters
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