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Dendritic Cell Therapy

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https://www.readbyqxmd.com/read/29163786/axl-inhibition-induces-the-antitumor-immune-response-which-can-be-further-potentiated-by-pd-1-blockade-in-the-mouse-cancer-models
#1
Zhiqiang Guo, Yan Li, Dandan Zhang, Jiaying Ma
Immune checkpoint blockers (ICB) have emerged as a promising new class of antitumor agents which significantly change the treatment landscape in a range of tumors; however, cancer patients benefited from ICB-based immunotherapy remains limited, scoring the need to explore the combination treatments with synergistic mechanisms of action. Axl receptor tyrosine kinase critically involves in the carcinogenesis of multiple cancers due to its dual roles in both promoting cancer invasion and metastasis and suppressing myeloid cell activation and function...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163518/mixed-signals-co-stimulation-in-invariant-natural-killer-t-cell-mediated-cancer-immunotherapy
#2
REVIEW
Susannah C Shissler, Michael S Lee, Tonya J Webb
Invariant natural killer T (iNKT) cells are an integral component of the immune system and play an important role in antitumor immunity. Upon activation, iNKT cells can directly kill malignant cells as well as rapidly produce cytokines that stimulate other immune cells, making them a front line defense against tumorigenesis. Unfortunately, iNKT cell number and activity are reduced in multiple cancer types. This anergy is often associated with upregulation of co-inhibitory markers such as programmed death-1...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163502/regulating-immunogenicity-and-tolerogenicity-of-bone-marrow-derived-dendritic-cells-through-modulation-of-cell-surface-glycosylation-by-dexamethasone-treatment
#3
Kevin Lynch, Oliver Treacy, Jared Q Gerlach, Heidi Annuk, Paul Lohan, Joana Cabral, Lokesh Joshi, Aideen E Ryan, Thomas Ritter
Dendritic cellular therapies and dendritic cell vaccines show promise for the treatment of autoimmune diseases, the prolongation of graft survival in transplantation, and in educating the immune system to fight cancers. Cell surface glycosylation plays a crucial role in the cell-cell interaction, uptake of antigens, migration, and homing of DCs. Glycosylation is known to change with environment and the functional state of DCs. Tolerogenic DCs (tDCs) are commonly generated using corticosteroids including dexamethasone, however, to date, little is known on how corticosteroid treatment alters glycosylation and what functional consequences this may have...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163499/fc%C3%AE%C2%B5ri-%C3%AE-chain-negatively-modulates-dectin-1-responses-in-dendritic-cells
#4
Yi-Gen Pan, Yen-Ling Yu, Chi-Chien Lin, Lewis L Lanier, Ching-Liang Chu
The inhibitory effect of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters DAP12 and FcεRI γ-chain (FcRγ) has been found in many immune functions. Herein, we have further explored the role of these adapters in C-type lectin receptors response. We identified that FcRγ, but not DAP12, could negatively regulate the Dectin-1 responses in dendritic cells (DCs). Loss of FcRγ or both DAP12 and FcRγ enhanced the maturation and cytokine production in DCs upon Dectin-1 activation compared to normal cells, whereas DCs lacking only DAP12 showed little changes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29158557/mir-29b-antagonizes-the-pro-inflammatory-tumor-promoting-activity-of-multiple-myeloma-educated-dendritic-cells
#5
C Botta, M Cucè, M R Pitari, D Caracciolo, A Gullà, E Morelli, C Riillo, L Biamonte, M E G Cantafio, R Prabhala, C Mignogna, A Di Vito, E Altomare, N Amodio, M T Di Martino, P Correale, M Rossi, A Giordano, N C Munshi, P Tagliaferri, P Tassone
Dendritic cells (DCs) play a key role in regulating tumor immunity, tumor cell growth and drug resistance. We hypothesized that multiple myeloma (MM) cells might recruit and reprogram DCs to a tumor-permissive phenotype by changes within their miRNA network. By analyzing 6 different miRNA-profiling datasets, miR-29b was identified as the only miRNA upregulated in normal mature DCs and significantly downregulated in tumor associated DCs. This finding was validated in primary DCs co-cultured in vitro with MM cell lines and in primary bone marrow DCs from MM patients...
November 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29155454/harnessing-the-power-of-regulatory-t-cells-to-control-autoimmune-diabetes-overview-and-perspective
#6
REVIEW
Hua Yu, Ricardo Paiva, Richard A Flavell
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease resulting in islet β-cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Although the mechanisms that initiate T1D still remain elusive, a breakdown of immune tolerance between effector T cells (Teff) and regulatory T cells (Treg) is considered to be the crucial component leading to autoimmunity. As such, strategies have been developed to boost the number and/or function of Treg in the hope of specifically hampering the pathogenic Teff activity...
November 20, 2017: Immunology
https://www.readbyqxmd.com/read/29151581/human-pbmc-transferred-murine-mhc-class-i-ii-deficient-nog-mice-enable-long-term-evaluation-of-human-immune-responses
#7
Tomonori Yaguchi, Asuka Kobayashi, Takashi Inozume, Kenji Morii, Haruna Nagumo, Hiroshi Nishio, Takashi Iwata, Yuyo Ka, Ikumi Katano, Ryoji Ito, Mamoru Ito, Yutaka Kawakami
Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses. However, when human peripheral blood mononuclear cells (PBMCs) are transferred into NOG (NOD/Shi-scid, IL-2rg(null)) mice, severe graft versus host disease (GVHD) hinders long term detailed analysis. Administration of human PBMCs into newly developed murine MHC class I- and class II-deficient NOG (NOG-dKO; NOG- Iab, B2m-double-knockout) mice showed sufficient engraftment of human immune cells with little sign of GVHD...
November 20, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29148731/conjugation-of-transforming-growth-factor-beta-to-antigen-loaded-poly-lactide-co-glycolide-nanoparticles-enhances-efficiency-of-antigen-specific-tolerance
#8
Liam M Casey, Ryan M Pearson, Kevin Hughes, Jeffrey Liu, Justin Rose, Madeleine G North, Leon Wang, Lei Mei, Stephen D Miller, Lonnie D Shea
Current strategies for treating autoimmunity involve the administration of broad-acting immunosuppressive agents that impair healthy immunity. Intravenous (i.v.) administration of poly(lactide-co-glycolide) nanoparticles (NPs) containing disease-relevant antigens (Ag-NPs) have demonstrated antigen(Ag)-specific immune tolerance in models of autoimmunity. However, subcutaneous (s.c.) delivery of Ag-NPs has not been effective. This investigation tested the hypothesis that co-delivery of the immunomodulatory cytokine, transforming growth factor beta 1 (TGF-β), on Ag-NPs would modulate the immune response to Ag-NPs and improve the efficiency of tolerance induction...
November 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29146441/combining-immunotherapies-for-the-treatment-of-prostate-cancer
#9
REVIEW
Jason M Redman, James L Gulley, Ravi A Madan
Sipuleucel-T, a therapeutic dendritic-cell vaccine, was Food and Drug Administration-approved for prostate cancer in 2010. No new immunotherapies for prostate cancer have been approved since. However, novel agents and combination approaches offer great promise for improving outcomes for prostate cancer patients. Here we review the latest developments in immunotherapy for prostate cancer. Sipuleucel-T has demonstrated a survival advantage of 4.1 months in metastatic castration-resistant prostate cancer. PSA-TRICOM (PROSTVAC), a prostate-specific antigen-targeted vaccine platform, showed evidence of clinical and immunologic efficacy in early-phase clinical trials, and results from a phase III trial in advanced disease are pending...
December 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29143804/telomeres-and-telomerase-in-hematopoietic-dysfunction-prognostic-implications-and-pharmacological-interventions
#10
REVIEW
Theresa Vasko, Andrea Kaifie, Matthias B Stope, Thomas Kraus, Patrick Ziegler
Leukocyte telomere length (TL) has been suggested as a marker of biological age in healthy individuals, but can also reflect inherited and acquired hematopoietic dysfunctions or indicate an increased turnover of the hematopoietic stem and progenitor cell compartment. In addition, TL is able to predict the response rate of tyrosine kinase inhibitor therapy in chronic myeloid leukemia (CML), indicates clinical outcomes in chronic lymphocytic leukemia (CLL), and can be used as screening tool for genetic sequencing of selected genes in patients with inherited bone marrow failure syndromes (BMFS)...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29143359/indolent-t-lymphoblastic-proliferation-concomitant-to-acinic-cell-carcinoma-mimicking-t-lymphoblastic-lymphoma-case-report-and-literature-review
#11
Hajime Yasuda, Miyuki Tsutsui, Yasunori Ota, Masaru Tanaka, Norio Komatsu
Indolent T-lymphoblastic proliferation (iT-LBP) is a non-clonal benign condition showing extrathymic proliferation of T-lymphoblasts positive for CD3, CD4, CD8, and TdT. Isolated iT-LBP has been observed, but the majority of iT-LBP have been seen in conjunction with other disorders including Castleman disease, hepatocellular carcinoma, follicular dendritic cell tumors, angioimmunoblastic T-cell lymphoma, myasthenia gravis, and acinic cell carcinoma (ACC). The clinical course of iT-LBP is indolent, and no therapy is usually required...
November 15, 2017: Histopathology
https://www.readbyqxmd.com/read/29143114/cancer-vaccine-strategies-translation-from-mice-to-human-clinical-trials
#12
REVIEW
Jay A Berzofsky, Masaki Terabe, Jane B Trepel, Ira Pastan, David F Stroncek, John C Morris, Lauren V Wood
We translated two cancer vaccine strategies from mice into human clinical trials. (1) In preclinical studies on TARP, an antigen expressed in most prostate cancers, we mapped epitopes presented by HLA-A*0201, modified them to increase affinity and immunogenicity in HLA transgenic mice, and induced human T cells that killed human cancer cells ("epitope enhancement"). In a clinical trial, HLA-A2(+) prostate cancer patients with PSA biochemical recurrence (Stage D0) were vaccinated with two peptides either in Montanide-ISA51 or on autologous dendritic cells (DCs)...
November 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29140820/renal-effects-of-cytokines-in-hypertension
#13
Yi Wen, Steven D Crowley
PURPOSE OF REVIEW: Inflammatory cytokines contribute to the pathogenesis of hypertension through effects on renal blood flow and sodium handling. This review will update recent advances that explore the renal actions of immune cells and cytokines in the pathogenesis of hypertension. RECENT FINDINGS: Populations of cells from both the innate and adaptive immune systems contribute to hypertension by modulating functions of the vasculature and epithelial cells in the kidney...
November 14, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29136520/characterization-of-myeloid-cell-populations-in-human-testes-collected-after-sex-reassignment-surgery
#14
Rosalie Ponte, Franck P Dupuy, Fadi Brimo, Vikram Mehraj, Pierre Brassard, Maud Belanger, Ekaterina Yurchenko, Mohammad-Ali Jenabian, Nicole F Bernard, Jean-Pierre Routy
The testis has been described in animal models as a site of immune privilege, which protects spermatids against tissue damage during inflammation. Myeloid cells, including macrophages and dendritic cells (DC), are defined as key players in the testicular immune privilege in animal models. However, their distribution and frequency in human testis remain poorly described. To overcome the challenges related to tissue sampling, we obtained testicular tissue from men under hormonal therapy who elected to have sex reassignment surgery (SRS)...
October 14, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29133434/pkd1-promotes-functional-synapse-formation-coordinated-with-n-cadherin-in-hippocampus
#15
Cheng Cen, Li-Da Luo, Wen-Qi Li, Gang Li, Na-Xi Tian, Ge Zheng, Dong-Min Yin, Yimin Zou, Yun Wang
Functional synapse formation is critical for the wiring of neural circuits in the developing brain. The cell adhesion molecule N-cadherin plays important roles in target recognition and synaptogenesis. However, the molecular mechanisms that regulate the localization of N-cadherin and the subsequent effects remain poorly understood. Here, we show that protein kinase D1 (PKD1) directly binds to N-cadherin at amino acid residues 836-871 and phosphorylates it at Ser 869, 871, 872, thereby increasing the surface localization of N-cadherin and promoting functional synapse formation in primary cultured hippocampal neurons obtained from embryonic day 18 rat embryos of either sex...
November 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29131413/the-effect-of-epitope-based-ligation-of-icam-1-on-survival-and-retransplantation-of-pig-islets-in-nonhuman-primates
#16
Jae-Il Lee, Jiyeon Kim, Yun-Jung Choi, Hi-Jung Park, Hye-Jin Park, Hae Joo Wi, Sunok Yoon, Jun-Seop Shin, Jin Kyun Park, Kyeong Cheon Jung, Eun Bong Lee, Hee Jung Kang, Eung Soo Hwang, Sang-Joon Kim, Chung-Gyu Park, Seong Hoe Park
BACKGROUND: Pig islet xenotransplantation is a promising alternative to allogeneic transplantation. However, the wide immunologic barrier between pigs and primates limits the long-term survival of the graft. MD-3, a novel monoclonal antibody (mAb) that recognizes a particular epitope of human ICAM-1, can render T cells tolerant to a xenograft by arresting dendritic cell maturation. We report the long-term survival of adult wild-type pig islets and successful retransplantation in nonhuman primates using a protocol comprising induction with MD-3 mAb and maintenance with anti-CD154 mAb and sirolimus...
November 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29130617/dendritic-cell-phenotype-in-severe-asthma-reflects-clinical-responsiveness-to-glucocorticoids
#17
Emma S Chambers, Alexandra M Nanzer, Paul E Pfeffer, David F Richards, Adrian R Martineau, Christopher J Griffiths, Christopher J Corrigan, Catherine M Hawrylowicz
BACKGROUND: Subsets of patients with severe asthma remain symptomatic despite prolonged, high dosage glucocorticoid therapy. We hypothesised that the clinical glucocorticoid sensitivity of these asthmatics is reflected in differences in peripheral blood dendritic cell subsets. OBJECTIVE: To compare peripheral blood leukocyte populations using flow cytometry at baseline and after 2 weeks of systemic glucocorticoid (steroid) treatment to identify immunological differences between steroid sensitive (SS) and steroid resistant (SR) asthmatics...
November 11, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29129094/rational-combination-of-immunotherapy-for-triple-negative-breast-cancer-treatment
#18
Chia-Wei Li, Seung-Oe Lim, Jennifer L Hsu, Mien-Chie Hung
Recent evidence indicates that tumor infiltrating lymphocytes (TILs), including cytotoxic T cells, are present in the tumor microenvironment of triple-negative breast cancers (TNBC). Despite the presence of cytotoxic T cells, these tumors still develop, progress, and metastasize, suggesting evasion of immune response. One mechanism of immunosuppression is the presence of the T cell inhibitory molecule, programmed death protein 1 (PD-1), on infiltrating T cells and its cognate ligand programmed death ligand 1 (PD-L1) on tumor cells, myeloid dendritic cells (DCs), and macrophages, in the tumor microenvironment...
October 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29127585/the-regulation-effect-of-ampk-in-immune-related-diseases
#19
REVIEW
Jing Wang, Zhenyu Li, Li Gao, Yanshuang Qi, Haibo Zhu, Xuemei Qin
AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that plays a key role in energetic metabolism regulation. Metabolic changes in immune cells, such as dendritic cell (DC), macrophages, neutrophils and lymphocytes that participate in the signal directed programs that promote or inhibit immune mediated diseases, including cancer, atherosclerosis and inflammatory diseases. Multiple pathogenic mechanisms are involved in the initiation and progression of disease, and many pathways have been uncovered...
November 8, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29126878/dendritic-cells-in-systemic-sclerosis-advances-from-human-and-mice-studies
#20
REVIEW
Alsya J Affandi, Tiago Carvalheiro, Timothy R D J Radstake, Wioleta Marut
Systemic sclerosis (SSc) is a complex heterogeneous fibrotic autoimmune disease with an unknown exact etiology, and characterized by three hallmarks: fibrosis, vasculopathy, and immune dysfunction. Dendritic cells (DCs) are specialized cells in pathogen sensing with high potency of antigen presentation and capable of releasing mediators to shape the immune response. Altered DCs distributions and their impaired functions may account for their role in breaking the immune tolerance and driving inflammation in SSc, and the direct contribution of DCs in promoting endothelial dysfunction and fibrotic process has only begun to be understood...
November 7, 2017: Immunology Letters
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