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Lymphocyte exhaustion

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https://www.readbyqxmd.com/read/28530712/the-microrna-mir-31-inhibits-cd8-t-cell-function-in-chronic-viral-infection
#1
Howell F Moffett, Adam N R Cartwright, Hye-Jung Kim, Jernej Godec, Jason Pyrdol, Tarmo Äijö, Gustavo J Martinez, Anjana Rao, Jun Lu, Todd R Golub, Harvey Cantor, Arlene H Sharpe, Carl D Novina, Kai W Wucherpfennig
During infection, antigen-specific T cells undergo tightly regulated developmental transitions controlled by transcriptional and post-transcriptional regulation of gene expression. We found that the microRNA miR-31 was strongly induced by activation of the T cell antigen receptor (TCR) in a pathway involving calcium and activation of the transcription factor NFAT. During chronic infection with lymphocytic choriomeningitis virus (LCMV) clone 13, miR-31-deficent mice recovered from clinical disease, while wild-type mice continued to show signs of disease...
May 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28488141/elevated-t-cell-activation-score-is-associated-with-improved-survival-of-breast-cancer
#2
Lingeng Lu, Yalai Bai, Zuoheng Wang
PURPOSE: Immune checkpoints cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death 1 receptor (PD-1) negatively regulate CD8(+) T cell functions, impeding the capacity of effector T cells to kill tumors. Here, we study the prognostic significance of CTLA4, PD-1 and T cell activation status in breast cancer. METHODS: Using a publicly accessed RNA-seq dataset including 1087 breast cancer patients, we performed Kaplan-Meier survival curves and multivariate Cox regression models to evaluate the associations of CTLA4, PD-1, and weighted T cell activation score with patients' overall survival...
May 9, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28482391/-two-families-of-x-linked-lymphoproliferative-disease-type-1-characterized-by-agammaglobulinemia
#3
W Y Li, J S Chen, Q Zhao, R X Dai, Y P Wang, H Y Zhao, X M Chen, X H Xue, X Y Sun, X M Tang, Y Zhang, Y Ding, X D Zhao, Z Y Zhang
Objective: To investigate the clinical and immunological laboratory features, mutations in SH2D1A gene and SAP protein expression in four children of two families with X-linked lymphoproliferative disease type 1(XLP-1). Method: Four patients (Family A including Patient 1 and Patient 2, Family B including Patient 3 and Patient 4) and their maternal relatives were enrolled in this study. The clinical manifestation, EBV infection status and chest CT scan were analyzed. The absolute and relative numbers of lymphocyte subsets, T lymphocyte proliferative response, SAP protein expression were assessed by flow cytometry...
May 4, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/28482363/acute-hematological-and-inflammatory-responses-to-high-intensity-exercise-tests-impact-of-duration-and-mode-of-exercise
#4
L G Minuzzi, H M Carvalho, D T Brunelli, F Rosado, C R Cavaglieri, C E Gonçalves, J M Gaspar, L M Rama, A M Teixeira
The purpose of this study was to investigate the hematological and inflammatory responses to 4 maximal high-intensity protocols, considering energy expenditure in each test. 9 healthy volunteers performed 4 high-intensity exercise tests of short [Wingate (WANT); Repeated-sprints (RSA)] and long durations [Continuous VO2 test (VCONT); intermittent VO2 test (VINT)] in a cycle-ergometer, until exhaustion. Hematological parameters and IL-6, IL-10 and creatine kinase (CK) levels were determined before (PRE), POST, 30 min, 1, 2, 12 and 24 h after the end of the protocols...
May 8, 2017: International Journal of Sports Medicine
https://www.readbyqxmd.com/read/28478837/the-spread-of-ebv-to-ectopic-lymphoid-aggregates-may-be-the-final-common-pathway-in-the-pathogenesis-of-me-cfs
#5
Willy Eriksen
According to the hypothesis presented here, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develops over 3 steps: Step 1 is characterized by the aggregation of lymphoid cells in dorsal root ganglia or other nervous structures. The cause of this formation of ectopic lymphoid aggregates may be an acute infection, asymptomatic reactivations of a common neurotropic virus, exposure to a neurotoxin, or physical injury to peripheral nerves. In step 2, Epstein-Barr virus (EBV)-infected lymphocytes or monocytes bring EBV from the circulation to one or several of these lymphoid aggregates, whereupon cell-to-cell transmission of EBV and proliferation of latently EBV-infected lymphocytes lead to the presence of many EBV-infected cells in the lymphoid aggregates...
May 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28474673/single-cell-rna-seq-enables-comprehensive-tumour-and-immune-cell-profiling-in-primary-breast-cancer
#6
Woosung Chung, Hye Hyeon Eum, Hae-Ock Lee, Kyung-Min Lee, Han-Byoel Lee, Kyu-Tae Kim, Han Suk Ryu, Sangmin Kim, Jeong Eon Lee, Yeon Hee Park, Zhengyan Kan, Wonshik Han, Woong-Yang Park
Single-cell transcriptome profiling of tumour tissue isolates allows the characterization of heterogeneous tumour cells along with neighbouring stromal and immune cells. Here we adopt this powerful approach to breast cancer and analyse 515 cells from 11 patients. Inferred copy number variations from the single-cell RNA-seq data separate carcinoma cells from non-cancer cells. At a single-cell resolution, carcinoma cells display common signatures within the tumour as well as intratumoral heterogeneity regarding breast cancer subtype and crucial cancer-related pathways...
May 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28434981/protein-transport-inhibitors-downregulate-the-expression-of-lag-3-on-regulatory-t-cells
#7
Sara Anvari, Andrea Grimbergen, Carla M Davis, George Makedonas
Modern immunologic studies demand increasing complexity because of a need to improve our understanding of the relationship between a cell's phenotype and its function. Regulatory T cells have been defined by a narrow set of phenotypic markers, however their actual functional capacity has not been determined at the single-cell level. Although the lymphocyte activation gene 3 (LAG-3; CD223) is a key marker for the identification of exhausted T cells, it may be useful also in resolving Treg subpopulations by indicating distinct functional breadths...
April 20, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28433478/investigation-on-acute-effects-of-enzyme-replacement-therapy-and-influence-of-clinical-severity-on-physiological-variables-related-to-exercise-tolerance-in-patients-with-late-onset-pompe-disease
#8
Annalisa Sechi, Desy Salvadego, Alessandro Da Ponte, Nicole Bertin, Andrea Dardis, Silvia Cattarossi, Grazia Devigili, Federico Reccardini, Bruno Bembi, Bruno Grassi
Exercise intolerance is one of the clinical hallmarks of late-onset Pompe disease (LOPD). We studied the acute effects of ERT on the physiological variables associated with exercise tolerance in patients chronically ERT treated. Moreover, we assessed the influence of clinical severity on the investigated variables. The day before (B) and the day after (A) ERT injection, 11 LOPD patients performed on a cycle-ergometer an exercise tolerance test to voluntary exhaustion; VO2, HR, RPE, and GAA activity were determined in B and A...
March 10, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28423678/influence-of-ipilimumab-on-expanded-tumour-derived-t-cells-from-patients-with-metastatic-melanoma
#9
Jon Bjoern, Rikke Lyngaa, Rikke Andersen, Lisbet Hölmich Rosenkrantz, Sine Reker Hadrup, Marco Donia, Inge Marie Svane
INTRODUCTION: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy (ACT) is a promising treatment for patients with advanced melanoma. Retrospective studies suggested an association between previous treatment with anti-CTLA-4 antibodies and long term survival after subsequent ACT. Thus, we hypothesized that treatment with anti-CTLA-4 antibodies can induce favourable changes to be detected in TILs. RESULTS: Expanded T cells from Ipilimumab treated patients had a higher proportion of cells expressing CD27, intracellular CTLA-4, TIM-3 and LAG-3...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421069/engineering-chimeric-antigen-receptor-t-cells-for-racing-in-solid-tumors-don-t-forget-the-fuel
#10
REVIEW
Melita Irving, Romain Vuillefroy de Silly, Kirsten Scholten, Nahzli Dilek, George Coukos
T-cells play a critical role in tumor immunity. Indeed, the presence of tumor-infiltrating lymphocytes is a predictor of favorable patient prognosis for many indications and is a requirement for responsiveness to immune checkpoint blockade therapy targeting programmed cell death 1. For tumors lacking immune infiltrate, or for which antigen processing and/or presentation has been downregulated, a promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell therapy. CARs are hybrid receptors that link the tumor antigen specificity and affinity of an antibody-derived single-chain variable fragment with signaling endodomains associated with T-cell activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28379266/keto-analogues-and-amino-acids-supplementation-induces-a-decrease-of-white-blood-cell-counts-and-a-reduction-of-muscle-damage-during-intense-exercise-under-thermoneutral-conditions
#11
R C P Lima, S R A S Camerino, T C L França, D S A Rodrigues, M G S Gouveia, A Ximenes-da-Silva, A Bassini, E S Prado, L C Cameron
This study evaluated the acute effect of keto analogue and amino acid (AA-KAAA) supplementation on both white blood cell counts and the established biomarkers of muscle damage during exercise under thermoneutral conditions. Sixteen male cyclists received a ketogenic diet for two days and were divided into two equal groups: a group taking AA-KAAA (KA) or a control group (PL). The athletes performed a two hour cycling session followed by a maximum incremental test until voluntary exhaustion (VExh). Blood samples were obtained at rest and during exercise for further hematological and biochemical analyses...
April 19, 2017: Food & Function
https://www.readbyqxmd.com/read/28375543/cd8-t-cell-regulation-by-t-regulatory-cells-and-the-programmed-cell-death-protein-1-pathway
#12
REVIEW
Pablo Penaloza-MacMaster
The primary function of the immune system is to protect the host from infectious microorganisms and cancers. However, a major component of the immune response involves the direct elimination of cells in the body and the induction of systemic inflammation, which may result in life-threatening immunopathology. Therefore, the immune system has developed complex mechanisms to regulate itself with a specialized subset of CD4 T lymphocytes (referred to as regulatory T cells) and immune checkpoint pathways, such as the programmed cell death protein 1 pathway...
June 2017: Immunology
https://www.readbyqxmd.com/read/28344863/tumor-infiltrating-lymphocytes-tils-from-patients-with-glioma
#13
Zhenjiang Liu, Qingda Meng, Jiri Bartek, Thomas Poiret, Oscar Persson, Lalit Rane, Elena Rangelova, Christopher Illies, Inti Harvey Peredo, Xiaohua Luo, Martin Vijayakumar Rao, Rebecca Axelsson Robertson, Ernest Dodoo, Markus Maeurer
Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21. Intracellular cytokine staining (ICS, IL-2, IL-17, TNFα and IFNγ production) as well as a cytotoxicity assay was used to detect TIL reactivity against autologous tumor cells or shared tumor-associated antigens (TAAs; i...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28337208/natural-killer-cell-development-and-maturation-revisited-possible-implications-of-a-novel-distinct-lin-cd34-dnam-1-bright-cxcr4-cell-progenitor
#14
Federica Bozzano, Francesco Marras, Andrea De Maria
Since the first description of natural killer (NK) cells, the view on their role in innate immunity has evolved considerably. In addition to first-line defense against transformed and pathogen-infected autologous cells, NK cells contribute to modulate adaptive immune responses and in some cases acquire specialized functions, including exhausted, adaptive, and decidual NK cells. NK cells derive from CD34(+) progenitors, in vivo and in vitro; however, it is unclear whether the high phenotype diversity in vivo may be generated from these precursors alone...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28306177/frequency-and-functional-characterization-of-exhausted-cd8-t-cells-in-chronic-lymphocytic-leukemia
#15
Saeid Taghiloo, Esmaeil Allahmoradi, Mohsen Tehrani, Hadi Hossein-Nataj, Ramin Shekarriz, Ghasem Janbabaei, Saeid Abediankenari, Hossein Asgarian-Omran
OBJECTIVES: The phenotypic and functional properties of Tim-3(+) /PD-1(+) /CD8(+) cells as exhausted T cells were investigated in chronic lymphocytic leukemia (CLL). METHODS: Frequency of CD8(+) /Tim-3(+) /PD-1(+) exhausted cells was determined by flow cytometry. For functional analysis, magnetic beads-isolated CD8(+) T cells were stimulated with PHA and PMA/ionocymin to assess their proliferative responses and cytokine production by MTT and ELISA, respectively...
March 17, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28292435/obstacles-posed-by-the-tumor-microenvironment-to-t%C3%A2-cell-activity-a-case-for-synergistic-therapies
#16
REVIEW
Kristin G Anderson, Ingunn M Stromnes, Philip D Greenberg
T cell dysfunction in solid tumors results from multiple mechanisms. Altered signaling pathways in tumor cells help produce a suppressive tumor microenvironment enriched for inhibitory cells, posing a major obstacle for cancer immunity. Metabolic constraints to cell function and survival shape tumor progression and immune cell function. In the face of persistent antigen, chronic T cell receptor signaling drives T lymphocytes to a functionally exhausted state. Here we discuss how the tumor and its microenvironment influences T cell trafficking and function with a focus on melanoma, and pancreatic and ovarian cancer, and discuss how scientific advances may help overcome these hurdles...
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28289860/the-pd-l1-pd-1-pathway-promotes-dysfunction-but-not-exhaustion-in-tumor-responding-t-cells-from-pleural-effusions-in-lung-cancer-patients
#17
Heriberto Prado-Garcia, Susana Romero-Garcia, Alejandra Puerto-Aquino, Uriel Rumbo-Nava
Malignant pleural effusions are frequent in patients with advanced stages of lung cancer and are commonly infiltrated by lymphocytes and tumor cells. CD8+ T cells from these effusions have reduced effector functions. The programmed death receptor 1(PD-1)/programmed death ligand 1 (PD-L1) pathway is involved in T-cell exhaustion, and it might be responsible for T-cell dysfunction in lung cancer patients. Here, we show that PD-L1 is expressed on tumor cell samples from malignant effusions, on lung cancer cell lines, and, interestingly, on MRC-5 lung fibroblasts...
March 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28287115/efficient-control-of-chronic-lcmv-infection-by-a-cd4-t-cell-epitope-based-heterologous-prime-boost-vaccination-in-a-murine-model
#18
Ran He, Xinxin Yang, Cheng Liu, Xiangyu Chen, Lin Wang, Minglu Xiao, Jianqiang Ye, Yuzhang Wu, Lilin Ye
CD4(+) T cells are essential for sustaining CD8(+) T cell responses during a chronic infection. The adoptive transfer of virus-specific CD4(+) T cells has been shown to efficiently rescue exhausted CD8(+) T cells. However, the question of whether endogenous virus-specific CD4(+) T cell responses can be enhanced by certain vaccination strategies and subsequently reinvigorate exhausted CD8(+) T cells remains unexplored. In this study, we developed a CD4(+) T cell epitope-based heterologous prime-boost immunization strategy and examined the efficacy of this strategy using a mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection...
March 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28283662/exhaustion-associated-regulatory-regions-in-cd8-tumor-infiltrating-t-cells
#19
Giuliana P Mognol, Roberto Spreafico, Victor Wong, James P Scott-Browne, Susan Togher, Alexander Hoffmann, Patrick G Hogan, Anjana Rao, Sara Trifari
T-cell exhaustion is a progressive loss of effector function and memory potential due to persistent antigen exposure, which occurs in chronic viral infections and cancer. Here we investigate the relation between gene expression and chromatin accessibility in CD8(+) tumor-infiltrating lymphocytes (TILs) that recognize a model tumor antigen and have features of both activation and functional exhaustion. By filtering out accessible regions observed in bystander, nonexhausted TILs and in acutely restimulated CD8(+) T cells, we define a pattern of chromatin accessibility specific for T-cell exhaustion, characterized by enrichment for consensus binding motifs for Nr4a and NFAT transcription factors...
March 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28258692/lag3-cd223-as-a-cancer-immunotherapy-target
#20
REVIEW
Lawrence P Andrews, Ariel E Marciscano, Charles G Drake, Dario A A Vignali
Despite the impressive impact of CTLA4 and PD1-PDL1-targeted cancer immunotherapy, a large proportion of patients with many tumor types fail to respond. Consequently, the focus has shifted to targeting alternative inhibitory receptors (IRs) and suppressive mechanisms within the tumor microenvironment. Lymphocyte activation gene-3 (LAG3) (CD223) is the third IR to be targeted in the clinic, consequently garnering considerable interest and scrutiny. LAG3 upregulation is required to control overt activation and prevent the onset of autoimmunity...
March 2017: Immunological Reviews
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