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T-cell therapy

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https://www.readbyqxmd.com/read/29353058/chd7-is-critical-for-early-t-cell-development-and-thymus-organogenesis-in-zebrafish
#1
Zhi-Zhi Liu, Zi-Long Wang, Tae-Ik Choi, Wen-Ting Huang, Han-Tsing Wang, Ying-Ying Han, Lou-Yin Zhu, Hyun-Taek Kim, Jung-Hwa Choi, Jin-Soo Lee, Hyung-Goo Kim, Jian Zhao, Yue Chen, Zhuo Lu, Xiao-Li Tian, Bing-Xing Pan, Bao-Ming Li, Cheol-Hee Kim, Hong Xu
CHARGE syndrome is a congenital disorder affecting multiple organs and mainly caused by mutations in CHD7, a gene encoding a chromatin-remodeling protein. Immunodeficiency and reduced T-cells have been noted in CHARGE syndrome. However, the mechanisms underlying T-lymphopenia are largely unexplored. Here, we observed dramatic decrease of T cells in both chd7-knockdown and -knockout zebrafish embryos. Unexpectedly, hematopoietic stem and progenitor cells and, particularly, lymphoid progenitor cells were increased peripherally in nonthymic areas in chd7-deficient embryos, unlikely to contribute to the T cell decrease...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29352737/bronchiolitis-obliterans-syndrome-is-associated-with-increased-p-glycoprotein-expression-and-loss-of-glucocorticoid-receptor-from-steroid-resistant-pro-inflammatory-cd8-t-cells
#2
Greg Hodge, Sandra Hodge, Phan Tien Nguyen, Aeneas Yeo, Parama Sarkar, Arash Badiei, C L Holmes-Liew, Paul N Reynolds, Mark Holmes
Immunosuppressive therapy fails to suppress the production of pro-inflammatory cytokines, particularly by CD8+T cells, in stable lung transplant recipients and those undergoing chronic rejection, suggesting that some patients may become relatively resistant to immunosuppressants such as glucocorticoids (GC). We have shown loss of GC receptor (GCR) from the CD8+ cells, and we hypothesized that the drug membrane efflux pump, p-glycoprotein-1 (Pgp), may also be involved in lymphocyte steroid resistance following lung transplant...
January 20, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29352723/which-hiv-infected-adults-with-high-cd4-t-cell-counts-benefit-most-from-immediate-initiation-of-antiretroviral-therapy-a-post-hoc-subgroup-analysis-of-the-start-trial
#3
Jean-Michel Molina, Birgit Grund, Fred Gordin, Ian Williams, Mauro Schechter, Marcello Losso, Matthew Law, Ernest Ekong, Noluthando Mwelase, Athanasios Skoutelis, Martin J Wiselka, Linos Vandekerckhove, Thomas Benfield, David Munroe, Jens D Lundgren, James D Neaton
BACKGROUND: Immediate initiation of antiretroviral therapy (ART) in asymptomatic adults with CD4 counts higher than 500 cells per μL, as recommended, might not always be possible in resource-limited settings. We aimed to identify subgroups of individuals who would benefit most from immediate treatment. METHODS: The START trial was a randomised controlled trial in asymptomatic, HIV-positive adults previously untreated with ART. Participants with CD4 counts higher than 500 cells per μL were randomly assigned to receive immediate ART or to defer ART until CD4 counts were lower than 350 cells per μL...
January 15, 2018: Lancet HIV
https://www.readbyqxmd.com/read/29352713/clinical-variables-associated-with-overall-survival-in-metastatic-castration-resistant-prostate-cancer-patients-treated-with-sipuleucel-t-immunotherapy
#4
Xiao X Wei, Jaselle Perry, Emily Chang, Li Zhang, Robert A Hiatt, Charles J Ryan, Eric J Small, Lawrence Fong
BACKGROUND: Sipuleucel-T is an autologous cell-based cancer immunotherapy for men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its approval by the Food and Drug Administration was based on demonstration of an overall survival (OS) benefit in randomized placebo-controlled phase III trials. However, treatment was associated with a prostate-specific antigen (PSA) decline in only a small minority of patients. Understanding the clinical factors that are associated with OS could help guide treatment decisions, including patient selection and the timing of sipuleucel-T relative to other therapies...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29352515/principles-of-alemtuzumab-immunoablation-in-hematopoietic-cell-transplantation-for-non-malignant-diseases-in-children-a-review
#5
REVIEW
Gregory M T Guilcher, Ravi Shah, Shalini Shenoy
Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non-malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable...
January 19, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29352427/preserved-in-vitro-immunoreactivity-in-children-receiving-long-term-immunosuppressive-therapy-due-to-inflammatory-bowel-disease-or-autoimmune-hepatitis
#6
Teresa Schleker, Eva-Maria Jacobsen, Benjamin Mayer, Gudrun Strauss, Klaus-Michael Debatin, Carsten Posovszky
BACKGROUND: Children with inflammatory bowel disease (IBD) or autoimmune hepatitis (AIH) are at risk for severe infections. This is partially a result of their chronic disease condition but, moreover, a side effect of their immunosuppressive therapy. Currently, vaccinations with live vaccines are regarded as contraindicated under immunosuppressive therapy, mainly because of concerns about side effects and a lack of data showing an adequate immune reaction. As there is no systematic study on the individual immunoreactivity under immunosuppressive therapy in this patient group, we analyzed the lymphocyte subgroups and immunoreactivity of lymphocytes in children with IBD or AIH with and without immunosuppressive therapy in vitro...
January 19, 2018: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/29352298/hexokinase-ii-may-be-dispensable-for-cd4-t-cell-responses-against-a-virus-infection
#7
Siva Karthik Varanasi, Ujjaldeep Jaggi, Nissim Hay, Barry T Rouse
Activation of CD4 T cells leads to their metabolic reprogramming which includes enhanced glycolysis, catalyzed through hexokinase enzymes. Studies in some systems indicate that the HK2 isoform is the most up regulated isoform in activated T cells and in this report the relevance of this finding is evaluated in an infectious disease model. Genetic ablation of HK2 was achieved in only T cells and the outcome was evaluated by measures of T cell function. Our results show that CD4 T cells from both HK2 depleted and WT animals displayed similar responses to in vitro stimulation and yielded similar levels of Th1, Treg or Th17 subsets when differentiated in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29352292/rna-seq-of-kaposi-s-sarcoma-reveals-alterations-in-glucose-and-lipid-metabolism
#8
For Yue Tso, Andrew V Kossenkov, Salum J Lidenge, Owen Ngalamika, John R Ngowi, Julius Mwaiselage, Jayamanna Wickramasinghe, Eun Hee Kwon, John T West, Paul M Lieberman, Charles Wood
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352109/role-of-b-and-t-lymphocyte-attenuator-in-renal-transplant-recipients-with-biopsy-proven-acute-rejection
#9
Zijie Wang, Haiwei Yang, Xuzhong Liu, Jingying Zhang, Zhijian Han, Jun Tao, Chunchun Zhao, Xiaobin Ju, Ruoyun Tan, Min Gu
BACKGROUND Acute rejection is a common predisposing cause of allograft dysfunction in kidney transplantation. Recently, the B and T lymphocyte attenuator (BTLA)/herpes virus entry mediator (HVEM)/lymphotoxin (LIGHT)/CD160 pathway was found to be potentially involved in the regulation of T cell activation. This could mean that this pathway is involved in graft rejection in kidney transplantation; the present study aimed to explore this possibility. MATERIAL AND METHODS The expression of BTLA, HVEM, LIGHT and CD160 on peripheral CD4+, CD8+ and CD19+ lymphocytes were analyzed by flow cytometry in recipients with biopsy-proven acute rejection (BPAR) or stable allograft function, as well as in healthy volunteers...
January 20, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29352101/activation-of-disease-during-therapy-with-alemtuzumab-in-3-patients-with-multiple-sclerosis
#10
Thomas Wehrum, Lena-Alexandra Beume, Oliver Stich, Irina Mader, Mathias Mäurer, Adam Czaplinski, Cornelius Weiller, Sebastian Rauer
OBJECTIVE: To report 3 patients with multiple sclerosis showing severe activation of disease during immunotherapy with alemtuzumab. METHODS: Retrospective case series. RESULTS: Patient 1, a 21-year-old woman, developed severe cognitive impairment, sight deterioration, severe gait ataxia, urinary retention, and extensive progression of cerebral lesion load, including new lesions that exhibited gadolinium ring enhancement and dominance of CD19/20-positive B lymphocytes, 6 months after induction of alemtuzumab...
January 19, 2018: Neurology
https://www.readbyqxmd.com/read/29351987/cd83-is-a-new-potential-biomarker-and-therapeutic-target-for-hodgkin-lymphoma
#11
Ziduo Li, Xinsheng Ju, Kenneth Lee, Candice Clarke, Jennifer L Hsu, Edward Abadir, Christian E Bryant, Suzanne Pears, Neroli Sunderland, Scott Heffernan, Annemarie Hennessy, Tsun-Ho Lo, Geoffrey A Pietersz, Fiona Kupresanin, Phillip D Fromm, Pablo A Silveira, Con Tsonis, Wendy A Cooper, Ilona Cunningham, Christina Brown, Georgina J Clark, Derek N J Hart
Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. We demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to surrounding T cells and interestingly, the trogocytosing CD83+T cells expressed significantly more PD-1 compared to CD83- T cells...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351916/pathways-impacted-by-genomic-alterations-in-pulmonary-carcinoid-tumors
#12
Michael K Asiedu, Charles F Thomas, Jie Dong, Sandra C Schulte Tomaszek, Prasidda Khadka, Zhifu Sun, Farhad Kosari, Jin Jen, Julian R Molina, George Vasmatzis, Rui Kuang, Marie Christine Aubry, Ping Yang, Dennis A Wigle
PURPOSE: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% of all carcinoid malignancies, and are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The role of specific genomic alterations in the pathogenesis of pulmonary carcinoid tumors remains poorly understood. We sought to identify genomic alterations and pathways that are deregulated in these tumors to find novel therapeutic targets for pulmonary carcinoid tumors...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29351788/elevated-inflammatory-cytokines-in-aqueous-cytokine-profile-in-hiv-1-infected-patients-with-cataracts-in-uganda
#13
Juliet Otiti-Sengeri, Robert Colebunders, Steven J Reynolds, Musa Muwonge, Getrude Nakigozi, Valerian Kiggundu, Fred Nalugoda, Damalie Nakanjako
BACKGROUND: Cataracts occur earlier among HIV-infected adults and this is attributed to various intraocular inflammatory processes that result in early degeneration. In this study we purposed to investigate whether HIV infected individuals with cataracts develop heightened intraocular inflammatory processes compared to their HIV negative counterparts by determining the concentration of 8 cytokines in the aqueous humour of HIV-positive adults with cataracts and their HIV-negative counterparts...
January 19, 2018: BMC Ophthalmology
https://www.readbyqxmd.com/read/29351392/young-mice-expel-the-tapeworm-hymenolepis-diminuta-and-are-protected-from-colitis-by-triggering-a-memory-response-with-worm-antigen
#14
Toshio Arai, Fernando Lopes, Adam Shute, Arthur Wang, Derek M McKay
Infection with helminth parasites reduces the severity of concomitant inflammatory disease in adult mice. There is an alarming increase of IBD in children. It is important to determine if helminth therapy would be of value in pediatric IBD, and if triggering immunological memory to the worm would be anti-colitic. Three-week (young) and eight-week (adult) old Balb/c mice were infected with H. diminuta, and infectivity and T helper (TH)-2 immunity assessed. Other mice received H. diminuta {plus minus} a crude worm extract (HdE) 28-42 days post-infection (dpi) {plus minus} dinitrobenzene sulphonic acid (DNBS; 1...
January 4, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29350470/specific-expression-of-pd-l1-in-rela-fusion-supratentorial-ependymoma-implications-for-pd-1-targeted-therapy
#15
Davis A Witt, Andrew M Donson, Vladimir Amani, Daniel C Moreira, Bridget Sanford, Lindsey M Hoffman, Michael H Handler, Jean M Mulcahy Levy, Kenneth L Jones, Anandani Nellan, Nicholas K Foreman, Andrea M Griesinger
BACKGROUND: A desperate need for novel therapies in pediatric ependymoma (EPN) exists, as chemotherapy remains ineffective and radiotherapy often fails. EPN have significant infiltration of immune cells, which correlates with outcome. Immune checkpoint inhibitors provide an avenue for new treatments. This study characterizes tumor-infiltrating immune cells in EPN and aims at predicting candidates for clinical trials using checkpoint inhibitors targeting PD-L1/PD-1 (programmed death ligand 1/programmed death 1)...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29349709/the-host-response-in-critically-ill-sepsis-patients-on-statin-therapy-a-prospective-observational-study
#16
Maryse A Wiewel, Brendon P Scicluna, Lonneke A van Vught, Arie J Hoogendijk, Aeilko H Zwinderman, René Lutter, Janneke Horn, Olaf L Cremer, Marc J Bonten, Marcus J Schultz, Tom van der Poll
BACKGROUND: Statins can exert pleiotropic anti-inflammatory, vascular protective and anticoagulant effects, which in theory could improve the dysregulated host response during sepsis. We aimed to determine the association between prior statin use and host response characteristics in critically ill patients with sepsis. METHODS: We performed a prospective observational study in 1060 patients admitted with sepsis to the mixed intensive care units (ICUs) of two hospitals in the Netherlands between January 2011 and July 2013...
January 18, 2018: Annals of Intensive Care
https://www.readbyqxmd.com/read/29349573/mesencephalic-astrocyte-derived-neurotrophic-factor-manf-elevates-stimulus-evoked-release-of-dopamine-in-freely-moving-rats
#17
Juho-Matti Renko, Susanne Bäck, Merja H Voutilainen, T Petteri Piepponen, Ilkka Reenilä, Mart Saarma, Raimo K Tuominen
Neurotrophic factors (NTFs) hold potential as disease-modifying therapies for neurodegenerative disorders like Parkinson's disease. Glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), and mesencephalic astrocyte-derived neurotrophic factor (MANF) have shown neuroprotective and restorative effects on nigral dopaminergic neurons in various animal models of Parkinson's disease. To date, however, their effects on brain neurochemistry have not been compared using in vivo microdialysis...
January 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29348598/increased-diversity-with-reduced-diversity-evenness-of-tumor-infiltrating-t-cells-for-the-successful-cancer-immunotherapy
#18
Akihiro Hosoi, Kazuyoshi Takeda, Koji Nagaoka, Tamaki Iino, Hirokazu Matsushita, Satoshi Ueha, Shin Aoki, Kouji Matsushima, Masato Kubo, Teppei Morikawa, Kazutaka Kitaura, Ryuji Suzuki, Kazuhiro Kakimi
To facilitate the optimization of cancer immunotherapy lacking immune-related adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T-cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB, anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T-cells in the tumor were activated and expanded to a greater or lesser extent by these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD-1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB monotherapy...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348565/an-in-vitro-system-of-autologous-lymphocytes-culture-that-allows-the-study-of-homeostatic-proliferation-mechanisms-in-human-naive-cd4-t-cells
#19
Isaac Rosado-Sánchez, Amaia González-Magaña, María M Pozo-Balado, Inés Herrero-Fernández, María J Polaino, María M Rodríguez-Méndez, María Francisca González-Escribano, Manuel Leal, Yolanda M Pacheco
The size of peripheral T-cell pool is kept constant throughout life. However, a decline in lymphocyte numbers is a feature of several human disorders, in which fast and slow homeostatic proliferation play a crucial role. Several in vitro and in vivo models have been developed to study such processes. Nevertheless, self- and commensal- antigens, well-known triggers of homeostatic proliferation, have not been examined in these models. We have designed an in vitro culture of human T-cells exposed to rIL7 and autologous antigen-presenting cells (aAPC) that allows the simultaneous characterization of the different types of homeostatic proliferation...
January 18, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29348421/patients-over-40-years-old-with-precursor-t-cell-lymphoblastic-lymphoma-have-different-prognostic-factors-comparing-to-the-youngers
#20
Meng Dong, Xudong Zhang, Zhenzhen Yang, Shaoxuan Wu, Mijing Ma, Zhaoming Li, Yu Chang, Xinhua Wang, Ling Li, Xin Li, Mingzhi Zhang, Qingjiang Chen
This study aimed to analyze the clinical characteristics and prognostic factors of patients, divided into over 40-year-old group or not, with precursor T-cell lymphoblastic lymphoma (Pre-T-LBL). Based on the retrospective analysis of the clinical data of 59 patients with Pre-T-LBL during the period from December 2010 to December 2015, albumin level, anemia, pleural or pericardial effusion, protocol, therapy response, mediastinal mass, lactate dehydrogenase (LDH), and international prognostic index (IPI) or age-adjusted international prognostic index (aaIPI) were summarized...
January 18, 2018: Scientific Reports
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