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https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#1
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28912776/human-cd5-innate-lymphoid-cells-are-functionally-immature-and-their-development-from-cd34-progenitor-cells-is-regulated-by-id2
#2
Maho Nagasawa, Kristine Germar, Bianca Blom, Hergen Spits
Innate lymphoid cells (ILCs) have emerged as a key cell type involved in surveillance and maintenance of mucosal tissues. Mouse ILCs rely on the transcriptional regulator Inhibitor of DNA-binding protein 2 (Id2) for their development. Here, we show that Id2 also drives development of human ILC because forced expression of Id2 in human thymic progenitors blocked T cell commitment, upregulated CD161 and promyelocytic leukemia zinc finger (PLZF), and maintained CD127 expression, markers that are characteristic for human ILCs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28880903/functional-differences-between-pd-1-and-pd-1-cd4-effector-t-cells-in-healthy-donors-and-patients-with-glioblastoma-multiforme
#3
Brittany A Goods, Amanda L Hernandez, Daniel E Lowther, Liliana E Lucca, Benjamin A Lerner, Murat Gunel, Khadir Raddassi, Vlad Coric, David A Hafler, J Christopher Love
Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) have been highly successful in the treatment of cancer. While PD-1 expression has been widely investigated, its role in CD4+ effector T cells in the setting of health and cancer remains unclear, particularly in the setting of glioblastoma multiforme (GBM), the most aggressive and common form of brain cancer. We examined the functional and molecular features of PD-1+CD4+CD25-CD127+Foxp3-effector cells in healthy subjects and in patients with GBM...
2017: PloS One
https://www.readbyqxmd.com/read/28860827/clinical-applications-of-dendritic-cells-cytokine-induced-killer-cells-mediated-immunotherapy-for-pancreatic-cancer-an-up-to-date-meta-analysis
#4
Yucai Zhang, Xiaorui Zhang, Anqi Zhang, Ke Li, Kai Qu
PURPOSE: This study aimed to systematically evaluate the efficacy and safety of dendritic cells-cytokine-induced killer (DC-CIK) cells immunotherapy in treating pancreatic cancer (PC) patients. METHODS: Data were collected from published articles of clinical trials. Databases including Web of Science, EMBASE, PubMed, Cochrane Library, Wanfang, and CNKI were searched. The main outcome measures in this research included the overall response rate (ORR), disease control rate (DCR), overall survival (OS), patients' quality of life (QoL), immune function, and adverse events...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28855899/negative-correlation-between-circulating-cd4-foxp3-cd127-regulatory-t-cells-and-subsequent-antibody-responses-to-infant-measles-vaccine-but-not-diphtheria-tetanus-pertussis-vaccine-implies-a-regulatory-role
#5
Jorjoh Ndure, Fatou Noho-Konteh, Jane U Adetifa, Momodou Cox, Francis Barker, My Thanh Le, Lady C Sanyang, Adboulie Drammeh, Hilton C Whittle, Ed Clarke, Magdalena Plebanski, Sarah L Rowland-Jones, Katie L Flanagan
Regulatory T cells (Tregs) play a key homeostatic role by suppressing immune responses. They have been targeted in mouse and human cancer studies to improve vaccine immunogenicity and tumor clearance. A number of commercially available drugs and experimental vaccine adjuvants have been shown to target Tregs. Infants have high numbers of Tregs and often have poor responses to vaccination, yet the role Tregs play in controlling vaccine immunogenicity has not been explored in this age group. Herein, we explore the role of CD4(+)FOXP3(+)CD127(-) Tregs in controlling immunity in infant males and females to vaccination with diphtheria-tetanus-whole cell pertussis (DTP) and/or measles vaccine (MV)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28844471/remodeling-t-cell-compartments-during-anti-cd3-immunotherapy-of-type-1-diabetes
#6
S Alice Long, Jerill Thorpe, Kevan C Herold, Mario Ehlers, Srinath Sanda, Noha Lim, Peter S Linsley, Gerald T Nepom, Kristina M Harris
The immunological mechanism(s) of action whereby teplizumab preserves C-peptide levels in the progression of patients with recent onset type 1 diabetes (T1D) is still not well understood. In the present study, we evaluated the kinetics of T cell modulation in peripheral blood following two 14-day courses of teplizumab therapy one year apart in recent onset T1D participants in the AbATE clinical trial. Transient rises in PD-1+Foxp3+ Treg and potentially anergic (CD57-KLRG1-PD-1+) cells in the circulating CD4 T cell compartment were paralleled by more profound increases in circulating CD8 T cells with traits of exhaustion (CD57-KLRG1+PD-1+, TIGIT+KLRG1+, and persistent down-modulation of CD127)...
August 18, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28835079/-effect-of-concurrent-chemoradiotherapy-and-radiotherapy-alone-on-peripheral-myeloid-derived-suppressor-and-t-regulatory-cells-in-patients-with-nasopharyngeal-cancer
#7
X C Dai, L Q Liu, B H Wang, C M Wang, L Ma, W M Cao, E X Dai
Objective: To investigate the percentage of myeloid-derived suppressor cells (MDSC) and T regulatory cells (Treg) in peripheral blood of nasopharyngeal cancer (NPC) patients undergoing concurrent chemoradiotherapy or radiotherapy alone. Methods: Sixty NPC patients who received radiotherapy or concurrent chemoradiotherapy from September 2012 to November 2015 and 20 healthy individuals were included in this study. For the patients, the blood samples were collected at four time points: pre-radiation (Pre-RT), reaching a dose of 40 Gy (RT-40 Gy), finishing radiation (RT-finish) and three months after finishing radiation (3m-post-RT)...
August 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28833201/dynamics-of-regulatory-t-cells-tregs-in-patients-with-oral-squamous-cell-carcinoma
#8
Sadhna Aggarwal, Suresh C Sharma, Satya N Das
BACKGROUND AND OBJECTIVES: The immune dysfunction in oral squamous cell carcinoma (OSCC) patients is one of the major factors for growth and dissemination of tumor affecting disease-free survival. METHODS: The phenotypic and functional characteristics of Regulatory T (Treg ) CD4(+) CD25(+) FoxP3(+) subsets in OSCC patients were assessed by multicolor flow cytometry and its effector component (TGF-β) by Western blot and qRT-PCR. RESULTS: An increased (P < 0...
August 22, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28802588/t-cell-costimulation-blockade-promotes-transplantation-tolerance-in-combination-with-sirolimus-and-post-transplantation-cyclophosphamide-for-haploidentical-transplantation-in-children-with-severe-aplastic-anemia
#9
Sarita Rani Jaiswal, Prakash Bhakuni, Shamsuz Zaman, Satish Bansal, Priyanka Bharadwaj, Sneh Bhargava, Suparno Chakrabarti
We conducted a pilot study employing extended T cell costimulation blockade (COSBL) with Abatacept along with sirolimus and post-transplantation cyclophosphamide (PTCy) in 10 patients (median age 12) with severe aplastic anemia (SAA). Nine patients engrafted in the COSBL group, compared to all 10 patients (median 14 vs 13days) treated on PTCy protocols without abatacept (CONTROL group). The incidence of acute graft-versus-host disease (GVHD) was 10.5% in the COSBL group compared to 50% in the CONTROL group (p=0...
August 9, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28801292/-oxidized-low-density-lipoprotein-modulates-differentiation-of-murine-memory-cd8-t-cell-subpopulations
#10
Hua Zheng, Ze-Hang Lin, Yan-Mei Zhang, Chen-Fei Zhou, Xuan Liu, Sha Wu
OBJECTIVE: To investigate effect of oxidized low-density lipoprotein (ox-LDL) on memory CD8(+) T cell subpopulation differentiation in mice with autoimmune diabetes. METHODS: Cultured splenic CD8(+) T cells from pre-diabetic NOD mice isolated with magnetic beads were treated with 30 µg/mL ox-LDL and 10 U/mL interleukin-2 (IL-2) for 24 h and the control cells were treated with IL-2 only. Flow cytometry was used to determine the percentage of splenic CD8(+)IFN-γ(+) T cells, expressions of CD8, CD44 and CD62L on the T cells, and the activation of T cell factor-1 (TCF-1) and STAT-3...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28759799/quantitative-and-qualitative-analysis-of-regulatory-t-cells-in-b-cell-chronic-lymphocytic-leukemia
#11
Vassiliki E Mpakou, Heleni-Dikaia Ioannidou, Eugene Konsta, Myrofora Vikentiou, Aris Spathis, Frieda Kontsioti, Christos K Kontos, Athanassios D Velentzas, Sotiris Papageorgiou, Diamantina Vasilatou, Konstantinos Gkontopoulos, Irene Glezou, Georgia Stavroulaki, Efthimia Mpazani, Stella Kokkori, Elias Kyriakou, Petros Karakitsos, George Dimitriadis, Vasiliki Pappa
Accumulated data indicate a significant role of T cell dysfunction in the pathogenesis of chronic lymphocytic leukemia. In CLL, regulatory T cells are significantly higher and show lower apoptotic levels compared to healthy donors. We demonstrate that CLL derived CD4(+)CD25(-)CD127(-) and CD4(+)CD25(low)CD127(-) subpopulations share a common immunophenotypic profile with conventional Tregs and are associated with advanced stage disease. We further provide evidence that the increased number of Tregs contributes indirectly to the proliferation of the CLL clone, by suppressing the proliferation of Teffs which in turn suppress CLL cells...
September 2017: Leukemia Research
https://www.readbyqxmd.com/read/28757397/low-utility-of-serum-25-hydroxyvitamin-d3-and-1-25-dihydroxyvitamin-d3-in-predicting-peripheral-treg-and-th17-cell-counts-in-esrd-and-renal-transplant-patients
#12
Mostafa G Aly, Li Zhu, Rolf Weimer, Gerhard Opelz, Christian Morath, Ruben Kuon, Mohammed Tohamy, Gamal Saadi, Mona Soliman, Walaa Ibrahim, Volker Daniel
BACKGROUND: Vitamin D has shown an immune-modulatory effect in different studies. Vitamin D stimulates Tregs and inhibits Th17 cells. The immune-modulatory role of vitamin D in chronic kidney disease (CKD) and renal transplant patients is unclear. We measured whether different serum levels of vitamin D were associated with an increased or decreased presence of lymphocyte subsets including Treg and Th17 cells in end-stage renal disease (ESRD) and renal transplant recipients. METHODS: Eighty-seven renal transplant recipients and 53 end-stage renal disease (ESRD) patients were enrolled in this study...
July 27, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28747257/cells-with-treg-specific-foxp3-demethylation-but-low-cd25-are-prevalent-in-autoimmunity
#13
Ricardo C Ferreira, Henry Z Simons, Whitney S Thompson, Daniel B Rainbow, Xin Yang, Antony J Cutler, Joao Oliveira, Xaquin Castro Dopico, Deborah J Smyth, Natalia Savinykh, Meghavi Mashar, Tim J Vyse, David B Dunger, Helen Baxendale, Anita Chandra, Chris Wallace, John A Todd, Linda S Wicker, Marcin L Pekalski
Identification of alterations in the cellular composition of the human immune system is key to understanding the autoimmune process. Recently, a subset of FOXP3(+) cells with low CD25 expression was found to be increased in peripheral blood from systemic lupus erythematosus (SLE) patients, although its functional significance remains controversial. Here we find in comparisons with healthy donors that the frequency of FOXP3(+) cells within CD127(low)CD25(low) CD4(+) T cells (here defined as CD25(low)FOXP3(+) T cells) is increased in patients affected by autoimmune disease of varying severity, from combined immunodeficiency with active autoimmunity, SLE to type 1 diabetes...
July 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28746881/mass-cytometric-analysis-of-hiv-entry-replication-and-remodeling-in-tissue-cd4-t-cells
#14
Marielle Cavrois, Trambak Banerjee, Gourab Mukherjee, Nandhini Raman, Rajaa Hussien, Brandon Aguilar Rodriguez, Joshua Vasquez, Matthew H Spitzer, Nicole H Lazarus, Jennifer J Jones, Christina Ochsenbauer, Joseph M McCune, Eugene C Butcher, Ann M Arvin, Nandini Sen, Warner C Greene, Nadia R Roan
To characterize susceptibility to HIV infection, we phenotyped infected tonsillar T cells by single-cell mass cytometry and created comprehensive maps to identify which subsets of CD4+ T cells support HIV fusion and productive infection. By comparing HIV-fused and HIV-infected cells through dimensionality reduction, clustering, and statistical approaches to account for viral perturbations, we identified a subset of memory CD4+ T cells that support HIV entry but not viral gene expression. These cells express high levels of CD127, the IL-7 receptor, and are believed to be long-lived lymphocytes...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28732046/qualitative-differences-in-cellular-immunogenicity-elicited-by-hepatitis-c-virus-t-cell-vaccines-employing-prime-boost-regimens
#15
Wendy G Tan, Iryna Zubkova, Alla Kachko, Frances Wells, Heiko Adler, Gerd Sutter, Marian E Major
T-cell based vaccines have been considered as attractive candidates for prevention of hepatitis C virus (HCV) infections. In this study we compared the magnitude and phenotypic characteristics of CD8+ T-cells induced by three commonly used viral vectors, Adenovirus-5 (Ad5), Vaccinia virus (VV) and Modified Vaccinia Ankara (MVA) expressing the HCV NS3/4A protein. C57/BL6 mice were primed with DNA expressing NS3/4A and boosted with each of the viral vectors in individual groups of mice. We then tracked the vaccine-induced CD8+ T-cell responses using pentamer binding and cytokine production analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28729148/clinical-grade-expanded-regulatory-t-cells-prevent-graft-versus-host-disease-while-allowing-a-powerful-t-cell-dependent-graft-versus-leukemia-effect-in-murine-models
#16
Beatrice Del Papa, Loredana Ruggeri, Elena Urbani, Stefano Baldoni, Debora Cecchini, Tiziana Zei, Roberta Iacucci Ostini, Barbara Crescenzi, Alessandra Carotti, Antonio Pierini, Paolo Sportoletti, Paolo Di Bartolomeo, Franca Falzetti, Cristina Mecucci, Andrea Velardi, Massimo F Martelli, Mauro Di Ianni
We developed a good manufacturing practices-compatible expansion protocol to improve number and purity of regulatory T cells (Tregs) available for clinical trials. Six clinical-grade separation procedures were performed, followed by expansion with high-dose interleukin (IL)-2, anti-CD3/anti-CD28 TCR stimulation, and rapamycin for 19 days achieving a median of 8.5-fold (range, 6.25 to 13.7) expansion. FOXP3 expression was stably maintained over the culture period, while the percentage of CD127 was significantly reduced...
July 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28720146/analysis-of-long-term-cd4-cd25highcd127-t-reg-cells-kinetics-in-peripheral-blood-of-lung-transplant-recipients
#17
Davide Piloni, Monica Morosini, Sara Magni, Alice Balderacchi, Luigia Scudeller, Emanuela Cova, Tiberio Oggionni, Giulia Stella, Carmine Tinelli, Filippo Antonacci, Andrea Maria D'Armini, Federica Meloni
BACKGROUND: The role of CD4(+)CD25(high)CD127(-) T-reg cells in solid-organ Transplant (Tx) acceptance has been extensively studied. In previous studies on kidney and liver recipients, peripheral T-reg cell counts were associated to graft survival, while in lung Tx, there is limited evidence for similar findings. This study aims to analyze long term peripheral kinetics of T-reg-cells in a cohort of lung recipients and tests its association to several clinical variables. METHODS: From jan 2009 to dec 2014, 137 lung Tx recipients were submitted to an immunological follow up (median: 105...
July 18, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28714519/circulating-regulatory-t-cell-subsets-predict-overall-survival-of-patients-with-unresectable-pancreatic-cancer
#18
Chen Liu, He Cheng, Guopei Luo, Yu Lu, Kaizhou Jin, Meng Guo, Quanxing Ni, Xianjun Yu
Most patients with pancreatic ductal adenocarcinoma (PDAC) have unresectable cancers with a dismal prognosis, in which cohort chemotherapy is the primary treatment. T cell immune adaption is critical for tumor immune escape and prognosis of this disease. The present study aimed to determine the correlation between peripheral T cell subset distribution in patients with unresectable PDAC and their response to chemotherapy. Two hundred and twelve patients with unresectable PDAC were included whose blood samples were collected for analysis of T cell subsets, including CD3+, CD4+, CD8+, CD8+CD28+ and CD4+CD25+CD127 T cells by flow cytometry before and after gemcitabine-based chemotherapy...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28686201/feeding-a-mixture-of-choline-forms-during-lactation-improves-offspring-growth-and-maternal-lymphocyte-response-to-ex-vivo-immune-challenges
#19
Erin D Lewis, Caroline Richard, Susan Goruk, Emily Wadge, Jonathan M Curtis, René L Jacobs, Catherine J Field
Study objectives were to examine the impact of feeding a mixture of choline forms, or a diet high in glycerophosphocholine (GPC) on maternal immune function and offspring growth during lactation. Lactating Sprague-Dawley rat dams (n = 6/diet) were randomized to one of three diets, providing 1 g/kg total choline: Control (100% free choline (FC)), Mixed Choline (MC; 50% phosphatidylcholine (PC), 25% FC, 25% GPC), or High GPC (HGPC; 75% GPC, 12.5% PC, 12.5% FC). At 3 weeks, cell phenotypes and cytokine production with Concanavalin A (ConA)-or lipopolysaccharide (LPS)-stimulated splenocytes and mesenteric lymphocytes were measured...
July 7, 2017: Nutrients
https://www.readbyqxmd.com/read/28683106/cytomegalovirus-infection-in-hiv-infected-and-uninfected-individuals-is-characterized-by-circulating-regulatory-t-cells-of-unconstrained-antigenic-specificity
#20
Adriana Tovar-Salazar, Adriana Weinberg
Cytomegalovirus (CMV) infection is associated with immune-suppression in immune-compromised hosts and old adults. We previously showed that ex vivo CMV restimulation of peripheral blood mononuclear cells (PBMC) of CMV-seropositive volunteers expanded CD4+CD27-CD28- regulatory T cells (Tregs). Here we evaluate the phenotype and function of circulating CD4+CD27-CD28- T cells of CMV-seropositive adults. Compared with CMV-seronegative, CMV-seropositive adults had 10-fold higher CD4+CD27-CD28-% T cells in PBMC. Circulating CD4+CD27-CD28- T cells from both CMV-seropositive and seronegative donors expressed higher levels of TGFβ, granzyme B, CD39, CD147 and IL-35, and lower levels of CD127, compared with their parent circulating CD4+ T cells...
2017: PloS One
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