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https://www.readbyqxmd.com/read/28526846/nk-cell-derived-il-10-is-critical-for-dc-nk-cell-dialogue-at-the-maternal-fetal-interface
#1
Sandra M Blois, Nancy Freitag, Irene Tirado-González, Shi-Bin Cheng, Markus M Heimesaat, Stefan Bereswill, Matthias Rose, Melanie L Conrad, Gabriela Barrientos, Surendra Sharma
DC-NK cell interactions are thought to influence the development of maternal tolerance and de novo angiogenesis during early gestation. However, it is unclear which mechanism ensures the cooperative dialogue between DC and NK cells at the feto-maternal interface. In this article, we show that uterine NK cells are the key source of IL-10 that is required to regulate DC phenotype and pregnancy success. Upon in vivo expansion of DC during early gestation, NK cells expressed increased levels of IL-10. Exogenous administration of IL-10 was sufficient to overcome early pregnancy failure in dams treated to achieve simultaneous DC expansion and NK cell depletion...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526681/adoptive-transfer-of-phosphoantigen-specific-%C3%AE-%C3%AE-t-cell-subset-attenuates-mycobacterium-tuberculosis-infection-in-nonhuman-primates
#2
Arwa Qaqish, Dan Huang, Crystal Y Chen, Zhuoran Zhang, Richard Wang, Shengpu Li, Enzhuoa Yang, Yang Lu, Michelle H Larsen, William R Jacobs, Lixia Qian, James Frencher, Ling Shen, Zheng W Chen
The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γδ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28526301/mfg-e8-reprogramming-of-macrophages-promotes-wound-healing-by-increased-bfgf-production-and-fibroblast-functions
#3
Patrick Laplante, Frédéric Brillant-Marquis, Marie-Joëlle Brissette, Benjamin Joannette-Pilon, Romain Cayrol, Victor Kokta, Jean-François Cailhier
Macrophages are essential for tissue repair. They have a crucial role in cutaneous wound healing, participating actively in the inflammation phase of the process. Unregulated macrophage activation may, however, represent a source of excessive inflammation leading to abnormal wound healing and hypertrophic scars. Our research group has demonstrated that apoptotic endothelial and epithelial cells secrete Milk Fat Globule Epidermal Growth Factor-8 (MFG-E8), which has the ability to reprogram macrophages from a M1 (pro-inflammatory) to a M2 (anti-inflammatory pro-repair) phenotype...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28525970/the-immunoregulatory-role-of-alpha-enolase-in-dendritic-cell-function-during-chlamydia-infection
#4
Khamia Ryans, Yusuf Omosun, Danielle N McKeithen, Tankya Simoneaux, Camilla C Mills, Nathan Bowen, Francis O Eko, Carolyn M Black, Joseph U Igietseme, Qing He
BACKGROUND: We have previously reported that interleukin-10 (IL-10) deficient dendritic cells (DCs) are potent antigen presenting cells that induced elevated protective immunity against Chlamydia. To further investigate the molecular and biochemical mechanism underlying the superior immunostimulatory property of IL-10 deficient DCs we performed proteomic analysis on protein profiles from Chlamydia-pulsed wild-type (WT) and IL-10(-/-) DCs to identify differentially expressed proteins with immunomodulatory properties...
May 19, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28518214/immune-monitoring-as-prerequisite-for-transplantation-tolerance-trials
#5
REVIEW
Katayoun Behnam Sani, Birgit Sawitzki
Ever since its first application in clinical medicine, scientists have urged to induce tolerance towards foreign allogeneic transplants and thus avoid rejection by the recipient's immune system. This would circumvent chronic use of immunosuppressive drugs (IS) and thus avoid development of IS-induced side effects, which are contributing to the still unsatisfactory long-term graft and patient survival after solid organ transplantation. Although manifold strategies of tolerance induction have been described in preclinical models, only three therapeutic approaches have been successfully utilized in a still small number of patients...
May 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28507809/t-cell-therapy-targeting-a-public-neoantigen-in-microsatellite-instable-colon-cancer-reduces-in-vivo-tumor-growth
#6
Else M Inderberg, Sébastien Wälchli, Marit R Myhre, Sissel Trachsel, Hilde Almåsbak, Gunnar Kvalheim, Gustav Gaudernack
T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to limit the risk of off-target toxicity. Directing T cells against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative to tumor-associated self-antigens. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507794/a-novel-nanobody-based-target-module-for-retargeting-of-t-lymphocytes-to-egfr-expressing-cancer-cells-via-the-modular-unicar-platform
#7
Susann Albert, Claudia Arndt, Anja Feldmann, Ralf Bergmann, Dominik Bachmann, Stefanie Koristka, Florian Ludwig, Pauline Ziller-Walter, Alexandra Kegler, Sebastian Gärtner, Marc Schmitz, Armin Ehninger, Marc Cartellieri, Gerhard Ehninger, Hans-Jürgen Pietzsch, Jens Pietzsch, Jörg Steinbach, Michael Bachmann
Recent treatments of leukemias with chimeric antigen receptor (CAR) expressing T cells underline their impressive therapeutic potential. However, once adoptively transferred into patients, there is little scope left to shut them down after elimination of tumor cells or in case adverse side effects occur. This becomes of special relevance if they are directed against commonly expressed tumor associated antigens (TAAs) such as receptors of the ErbB family. To overcome this limitation, we recently established a modular CAR platform technology termed UniCAR...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506464/recruited-monocytes-and-type-2-immunity-promote-lung-regeneration-following-pneumonectomy
#8
Andrew J Lechner, Ian H Driver, Jinwoo Lee, Carmen M Conroy, Abigail Nagle, Richard M Locksley, Jason R Rock
To investigate the role of immune cells in lung regeneration, we used a unilateral pneumonectomy model that promotes the formation of new alveoli in the remaining lobes. Immunofluorescence and single-cell RNA sequencing found CD115+ and CCR2+ monocytes and M2-like macrophages accumulating in the lung during the peak of type 2 alveolar epithelial stem cell (AEC2) proliferation. Genetic loss of function in mice and adoptive transfer studies revealed that bone marrow-derived macrophages (BMDMs) traffic to the lung through a CCL2-CCR2 chemokine axis and are required for optimal lung regeneration, along with Il4ra-expressing leukocytes...
May 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28504276/targeted-calcium-influx-boosts-cytotoxic-t-lymphocyte-function-in-the-tumour-microenvironment
#9
Kyun-Do Kim, Seyeon Bae, Tara Capece, Hristina Nedelkovska, Rafael G de Rubio, Alan V Smrcka, Chang-Duk Jun, Woojin Jung, Byeonghak Park, Tae-Il Kim, Minsoo Kim
Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4(+)CD25(+)Foxp3(+) regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca(2+) response...
May 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28502792/drug-binding-poses-relate-structure-with-efficacy-in-the-%C3%AE-opioid-receptor
#10
Katy J Sutcliffe, Graeme Henderson, Eamonn Kelly, Richard B Sessions
The μ-opioid receptor (MOPr) is a clinically important G protein-coupled receptor (GPCR) which couples to Gi/o proteins and arrestins. At present the receptor conformational changes that occur following agonist binding and activation are poorly understood. This study has employed molecular dynamics simulations to investigate the binding mode and receptor conformational changes induced by structurally similar opioid ligands of widely differing intrinsic agonist efficacy, norbuprenorphine, buprenorphine and diprenorphine...
May 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28502093/the-tlr4-trif-pathway-can-protect-against-the-development-of-experimental-allergic-asthma
#11
Karim H Shalaby, Saba Al-Heialy, Kimitake Tsuchiya, Soroor Farahnak, Toby K McGovern, Paul-Andre Risse, Woong-Kyung Suh, Salman T Qureshi, James G Martin
The Toll-like Receptor (TLR) adaptor proteins Myeloid Differentiating Factor 88 (MyD88) and Toll, interleukin-1 Receptor and Resistance protein (TIR) domain-containing adaptor inducing interferon-β (TRIF) comprise the two principal limbs of the TLR signaling network. We studied the role of these adaptors in the TLR4-dependent inhibition of allergic airway disease and induction of CD4+ICOS+ T cells by nasal application of Protollin(™) , a mucosal adjuvant composed of TLR2 and 4 agonists. Wild-type (wt), Trif -/- or Myd88 -/- mice were sensitized to birch pollen extract (BPEx), then received intranasal Protollin followed by consecutive BPEx challenges...
May 14, 2017: Immunology
https://www.readbyqxmd.com/read/28500072/the-upregulation-of-integrin-%C3%AE-d%C3%AE-2-cd11d-cd18-on-inflammatory-macrophages-promotes-macrophage-retention-in-vascular-lesions-and-development-of-atherosclerosis
#12
Moammir H Aziz, Kui Cui, Mitali Das, Kathleen E Brown, Christopher L Ardell, Maria Febbraio, Elzbieta Pluskota, Juying Han, Huaizhu Wu, Christie M Ballantyne, Jonathan D Smith, Martha K Cathcart, Valentin P Yakubenko
Macrophage accumulation is a critical step during development of chronic inflammation, initiating progression of many devastating diseases. Leukocyte-specific integrin αDβ2 (CD11d/CD18) is dramatically upregulated on macrophages at inflammatory sites. Previously we found that CD11d overexpression on cell surfaces inhibits in vitro cell migration due to excessive adhesion. In this study, we have investigated how inflammation-mediated CD11d upregulation contributes to macrophage retention at inflammatory sites during atherogenesis...
May 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28496990/mtorc1-regulates-mannose-6-phosphate-receptor-transport-and-t-cell-vulnerability-to-regulatory-t-cells-by-controlling-kinesin-kif13a
#13
Khawaja Ashfaque Ahmed, Jim Xiang
Mannose-6-phosphate receptor (M6PR) that facilitates cellular uptake of M6P-bearing proteins, including serine-protease granzyme-B (Gzm-B) has an important role in T-cell activation, migration and contraction. However, molecular mechanisms controlling M6PR expression in T cells remain poorly understood. Here, we show that M6PR expression on T cells is distinctively controlled by two common γ-chain cytokines interleukin-2 (IL-2) and IL-7, and the differential M6PR expression is not caused by an altered synthesis of M6PR protein, but is a result of distinct regulation of kinesin-3 motor-protein KIF13A that transport M6PR onto cell surfaces...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28495853/transgenerational-transmission-of-asthma-risk-after-exposure-to-environmental-particles-during-pregnancy
#14
David J Gregory, Lester Kobzik, Zhiping Yang, Connor C McGuire, Alexey V Fedulov
Exposure to environmental particles during pregnancy increases asthma susceptibility of the offspring. We tested the hypothesis that this transmission continues to F2 and F3 generations and occurs via epigenetic mechanisms. We compared allergic susceptibility of three generations of BALB/c offspring after a single maternal exposure during pregnancy to diesel exhaust particles or concentrated urban air particles. After pregnant dams received intranasal instillations of particle suspensions or control, their F1, F2 and F3 offspring were tested in a low-dose ovalbumin protocol for allergy sensitivity...
May 11, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28493549/transcription-factor-rbp-j-mediated-signaling-regulates-basophil-s-immunoregulatory-function-in-mouse-asthma-model
#15
Shuo-Yao Qu, Ya-Long He, Jian Zhang, Chang-Gui Wu
Basophils (BAs) play an important role in the promotion of aberrant Th2 immune response in asthma. It is not only the effective cell, but also modulates initiation of Th2 immune responses. We earlier demonstrated that Notch signaling regulates the biological function of BAs in vitro. However, whether this pathway plays the same role in vivo is not clear. The purpose of the present study was to investigate the effect of Notch signaling on BA's function in the regulation of allergic airway inflammation in a murine model of asthma...
May 11, 2017: Immunology
https://www.readbyqxmd.com/read/28490801/dendritic-cells-provide-a-therapeutic-target-for-synthetic-small-molecule-analogues-of-the-parasitic-worm-product-es-62
#16
Felicity E Lumb, James Doonan, Kara S Bell, Miguel A Pineda, Marlene Corbet, Colin J Suckling, Margaret M Harnett, William Harnett
ES-62, a glycoprotein secreted by the parasitic filarial nematode Acanthocheilonema viteae, subverts host immune responses towards anti-inflammatory phenotypes by virtue of covalently attached phosphorylcholine (PC). The PC dictates that ES-62 exhibits protection in murine models of inflammatory disease and hence a library of drug-like PC-based small molecule analogues (SMAs) was synthesised. Four sulfone-containing SMAs termed 11a, 11e, 11i and 12b were found to reduce mouse bone marrow-derived dendritic cell (DC) pathogen-associated molecular pattern (PAMP)-induced pro-inflammatory cytokine production, inhibit NF-κB p65 activation, and suppress LPS-induced up-regulation of CD40 and CD86...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28490441/pd-1-regulates-klrg1-group-2-innate-lymphoid-cells
#17
Samuel Taylor, Yuefeng Huang, Grace Mallett, Chaido Stathopoulou, Tania C Felizardo, Ming-An Sun, Evelyn L Martin, Nathaniel Zhu, Emma L Woodward, Martina S Elias, Jonathan Scott, Nick J Reynolds, William E Paul, Daniel H Fowler, Shoba Amarnath
Group 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens and maintain tissue homeostasis in response to cytokines. Positive regulation of ILC-2s through ICOS has been recently elucidated. We demonstrate here that PD-1 is an important negative regulator of KLRG1(+) ILC-2 function in both mice and humans. Increase in KLRG1(+) ILC-2 cell numbers was attributed to an intrinsic defect in PD-1 signaling, which resulted in enhanced STAT5 activation. During Nippostrongylus brasiliensis infection, a significant expansion of KLRG1(+) ILC-2 subsets occurred in Pdcd1(-/-) mice and, upon adoptive transfer, Pdcd1(-/-) KLRG1(+) ILC-2s significantly reduced worm burden...
May 10, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28489338/regulatory-t-cells-promote-natural-killer-cell-education-in-mixed-chimeras
#18
Benedikt Mahr, Nina Pilat, Svenja Maschke, Nicolas Granofszky, Christoph Schwarz, Lukas Unger, Karin Hock, Andreas M Farkas, Christoph Klaus, Heinz Regele, Thomas Wekerle
Therapeutic administration of regulatory T cells (Tregs) leads to engraftment of conventional doses of allogeneic bone marrow (BM) in non-irradiated recipient mice conditioned with costimulation blockade and mTOR inhibition. The mode of action responsible for this Treg effect is poorly understood but may encompass the control of costimulation blockade-resistant natural killer (NK) cells. We show that transient NK cell depletion at the time of BM transplantation (BMT) led to BM engraftment and persistent chimerism without Treg transfer, but failed to induce skin graft tolerance...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28488122/the-potential-of-cellular-and-viral-based-immunotherapies-for-malignant-glioma-dendritic-cell-vaccines-adoptive-cell-transfer-and-oncolytic-viruses
#19
REVIEW
Russell Maxwell, Andrew S Luksik, Tomas Garzon-Muvdi, Michael Lim
PURPOSE OF REVIEW: Malignant gliomas, including glioblastoma and anaplastic astrocytoma, are the most frequent primary brain tumors and present with many treatment challenges. In this review, we discuss the potential of cellular- and viral-based immunotherapies in the treatment of malignant glioma, specifically focusing on dendritic cell vaccines, adoptive cell therapy, and oncolytic viruses. RECENT FINDINGS: Diverse cellular- and viral-based strategies have been engineered and optimized to generate either a specific or broad antitumor immune response in malignant glioma...
June 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28486109/tumor-residing-batf3-dendritic-cells-are-required-for-effector-t-cell-trafficking-and-adoptive-t-cell-therapy
#20
Stefani Spranger, Daisy Dai, Brendan Horton, Thomas F Gajewski
Effector T cells have the capability of recognizing and killing cancer cells. However, whether tumors can become immune resistant through exclusion of effector T cells from the tumor microenvironment is not known. By using a tumor model resembling non-T cell-inflamed human tumors, we assessed whether adoptive T cell transfer might overcome failed spontaneous priming. Flow cytometric assays combined with intra-vital imaging indicated failed trafficking of effector T cells into tumors. Mechanistically, this was due to the absence of CXCL9/10, which we found to be produced by CD103(+) dendritic cells (DCs) in T cell-inflamed tumors...
May 8, 2017: Cancer Cell
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