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Lymphocyte exhaustion

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https://www.readbyqxmd.com/read/28929191/overview-of-lag-3-expressing-il-10-producing-regulatory-t-cells
#1
Keishi Fujio, Kazuhiko Yamamoto, Tomohisa Okamura
Regulatory T cells (Treg cells) play crucial roles in the induction of peripheral tolerance to self- and foreign-antigens. IL-10-producing regulatory T cells (IL-10-producing Treg cells) constitute a Treg cell subset characterized by the production of high amounts of IL-10, cytokine-mediated immunosuppressive capabilities, and independence of Foxp3 expression for their suppressive activity. In the past decade, identifying naturally occurring IL-10-producing Treg cells was difficult due to the lack of suitable surface markers...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28922790/the-balance-between-cytotoxic-t-cell-lymphocytes-and-immune-checkpoint-expression-in-the-prognosis-of-colon-tumors
#2
Laetitia Marisa, Magali Svrcek, Ada Collura, Etienne Becht, Pascale Cervera, Kristell Wanherdrick, Olivier Buhard, Anastasia Goloudina, Vincent Jonchère, Janick Selves, Gerard Milano, Dominique Guenot, Romain Cohen, Chrystelle Colas, Pierre Laurent-Puig, Sylviane Olschwang, Jérémie H Lefèvre, Yann Parc, Valérie Boige, Côme Lepage, Thierry André, Jean-François Fléjou, Valentin Dérangère, François Ghiringhelli, Aurélien de Reynies, Alex Duval
Background: Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore. Methods: The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI)...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28919989/cyclophosphamide-treatment-regulates-the-balance-of-functional-exhausted-tumor-specific-cd8-t-cells
#3
Aurélie Hanoteau, Coralie Henin, David Svec, Charlotte Bisilliat Donnet, Sébastien Denanglaire, Didier Colau, Pedro Romero, Oberdan Leo, Benoit Van den Eynde, Muriel Moser
An important question is how chemotherapy may (re-)activate tumor-specific immunity. In this study, we provide a phenotypic, functional and genomic analysis of tumor-specific CD8(+) T cells in tumor (P815)-bearing mice, treated or not with cyclophosphamide. Our data show that chemotherapy favors the development of effector-type lymphocytes in tumor bed, characterized by higher KLRG-1 expression, lower PD-1 expression and increased cytotoxicity. This suggests re-engagement of T lymphocytes into the effector program...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28904066/pd-1-status-in-cd8-t-cells-associates-with-survival-and-anti-pd-1-therapeutic-outcomes-in-head-and-neck-cancer
#4
Benjamin A Kansy, Fernando Concha-Benavente, Raghvendra M Srivastava, Hyun-Bae Jie, Gulidanna Shayan, Yu Lei, Jessica Moskovitz, Jennifer Moy, Jing Li, Sven Brandau, Stephan Lang, Nicole C Schmitt, Gordon J Freeman, William E Gooding, David A Clump, Robert L Ferris
Improved understanding of expression of immune checkpoint receptors (ICR) on tumor-infiltrating lymphocytes (TIL) may facilitate more effective immunotherapy in head and neck cancer (HNC) patients. A higher frequency of PD-1(+) TIL has been reported in human papillomavirus (HPV)(+) HNC patients, despite the role of PD-1 in T cell exhaustion. This discordance led us to hypothesize that the extent of PD-1 expression more accurately defines T cell function and prognostic impact, since PD-1(high) T cells may be more exhausted than PD-1(low) T cells and may influence clinical outcome and response to anti-PD-1 immunotherapy...
September 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28900926/immunological-disorders-regulation-of-ca-2-signaling-in-t-lymphocytes
#5
Sonal Srikanth, Jin Seok Woo, Zuoming Sun, Yousang Gwack
Engagement of T cell receptors (TCRs) with cognate antigens triggers cascades of signaling pathways in helper T cells. TCR signaling is essential for the effector function of helper T cells including proliferation, differentiation, and cytokine production. It also modulates effector T cell fate by inducing cell death, anergy (nonresponsiveness), exhaustion, and generation of regulatory T cells. One of the main axes of TCR signaling is the Ca(2+)-calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28899767/effects-of-hexavalent-chromium-on-mouse-splenic-t-lymphocytes
#6
Lu Dai, Wenhua Xu, Hui Li, Jacqueline A Frank, Caigu He, Zhuo Zhang, Gang Chen
Hexavalent chromium [Cr(VI)] is widely used in various industrial processes and has been recognized as a carcinogen. As the first line of host defense system, the immune system can be a primary target of Cr(VI). T cell population represents a major arm of the immune system that plays a critical role in host anti-tumor immunity. Dysfunction of T cells, such as exhaustion under the persistent presence of tumor antigen, compromise host anti-tumor immunity resulting in oncogenesis. Previous studies have shown Cr(VI) exposure alters the phenotype of human peripheral blood lymphocytes...
September 9, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28890294/analysis-of-non-small-cell-lung-cancer-microenvironment-indicates-preponderance-of-t-cell-exhaustion-marker-expression
#7
Hui Zhou, Tingwei Liu, Zanfeng Wang
Lung cancer metastasis causes 70% of an estimated 1.4 million deaths per annum. The major shortcoming in lung cancer is the tendency to have inherent or develop acquired resistance to chemotherapy. It is now evolving that such resistance might develop due to differential contribution and interaction with tumor microenvironment, stromal cells, and the extracellular matrix. The objective of the current study was to define the lung cancer tumor microenvironment. We have identified multiple tumor-infiltrating T lymphocyte subsets in patients with lung cancer, which were independent of disease stage...
September 7, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28878077/irf9-prevents-cd8-t-cell-exhaustion-in-an-extrinsic-manner-during-acute-lcmv-infection
#8
Magdalena Huber, Tamara Suprunenko, Thomas Ashhurst, Felix Marbach, Hartmann Raifer, Svenja Wolff, Thomas Strecker, Barney Viengkhou, So Ri Jung, Hannah-Lena Obermann, Stefan Bauer, Haifeng C Xu, Philipp Lang, Adomati Tom, Karl S Lang, Nicholas J C King, Iain L Campbell, Markus J Hofer
Effective CD8(+) T cell responses play an important role in determining the course of a viral infection. Overwhelming antigen exposure can result in suboptimal CD8(+) T cell responses, leading to chronic infection. This altered CD8(+) T cell differentiation state, termed exhaustion, is characterized by reduced effector function, upregulation of inhibitory receptors and altered expression of transcription factors. Prevention of overwhelming antigen exposure which limits CD8(+) T cell exhaustion is of significant interest for controlling chronic infection...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28859023/isolated-third-cranial-nerve-palsy-leading-to-the-diagnosis-of-disseminated-burkitt-lymphoma-a-case-report-and-literature-review
#9
Arens Taga, Marco Russo, Irene Florindo, Giovanni Pavesi
INTRODUCTION: Dysfunction of the third cranial nerve can result from lesions anywhere along its course between the midbrain and the orbit. Lymphoma is a rare cause of isolated oculomotor nerve palsy (OMP), with only 19 cases reported in the literature. We describe a case of an isolated OMP leading to the diagnosis of disseminated Burkitt lymphoma (BL). CASE REPORT: A 37-year-old man presented with acute onset diplopia and right ptosis and was found to have a right pupillary sparing OMP...
September 2017: Neurologist
https://www.readbyqxmd.com/read/28843991/imbalanced-immune-responses-involving-inflammatory-molecules-and-immune-related-pathways-in-the-lung-of-acute-and-subchronic-arsenic-exposed-mice
#10
Jinlong Li, Lu Zhao, Yang Zhang, Wei Li, Xiaoxu Duan, Jinli Chen, Yuanyuan Guo, Shan Yang, Guifan Sun, Bing Li
Inorganic arsenic has been claimed to increase the risk of pulmonary diseases through ingestion, as opposed to inhalation, which makes it a unique and intriguing environmental toxicant. However, the immunotoxic effects of lung, one of the targets of arsenic exposure, have not been extensively investigated in vivo. In the present study, we first confirmed that 2.5, 5 and 10mg/kg NaAsO2 orally for 24h dose-dependently triggered the infiltration of neutrophils, lymphocytes and macrophages in BALF. Not only the transcription activity, but also the secretion of proinflammatory cytokines IL-1β, IL-6 and TNF-α were consistently raised in the lung and BALF of acute arsenic-exposed mice...
August 24, 2017: Environmental Research
https://www.readbyqxmd.com/read/28842749/complement-as-a-regulator-of-adaptive-immunity
#11
REVIEW
Justin Killick, Gregoire Morisse, Dirk Sieger, Anne L Astier
The complement system is an ancient and evolutionarily conserved effector system comprising in mammals over 50 circulating and membrane bound proteins. Complement has long been described as belonging to the innate immune system; however, a number of recent studies have demonstrated its key role in the modulation of the adaptive immune response. This review does not set out to be an exhaustive list of the numerous interactions of the many complement components with adaptive immunity; rather, we will focus more precisely on the role of some complement molecules in the regulation of antigen presenting cells, as well as on their direct effect on the activation of the core adaptive immune cells, B and T lymphocytes...
August 25, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28791012/extracellular-vesicles-transfer-the-receptor-programmed-death-1-in-rheumatoid-arthritis
#12
Stinne R Greisen, Yan Yan, Aida S Hansen, Morten T Venø, Jens R Nyengaard, Søren K Moestrup, Malene Hvid, Gordon J Freeman, Jørgen Kjems, Bent Deleuran
INTRODUCTION: Extracellular vesicles (EVs) have been recognized as route of communication in the microenvironment. They transfer proteins and microRNAs (miRNAs) between cells, and possess immunoregulatory properties. However, their role in immune-mediated diseases remains to be elucidated. We hypothesized a role for EVs in the rheumatoid arthritis (RA) joint, potentially involving the development of T cell exhaustion and transfer of the co-inhibitory receptor programmed death 1 (PD-1)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28770269/the-pd-1-pd-l1-inhibitory-pathway-is-altered-in-primary-glomerulonephritides
#13
Ewelina Grywalska, Iwona Smarz-Widelska, Ewelina Krasowska-Zajac, Izabela Korona-Glowniak, Karolina Zaluska-Patel, Michal Mielnik, Martyna Podgajna, Anna Malm, Jacek Rolinski, Wojciech Zaluska
The pathogenesis of primary proliferative and non-proliferative glomerulonephritides (PGN and NPGN) is still not fully understood, however, current evidence suggests that most cases of PGN and NPGN are the results of immunologic response to different etiologic agents that activates various biological processes leading to glomerular inflammation and injury. Programmed cell death protein 1 (PD-1) is the major inhibitory receptor regulating T cell exhaustion. The aim of this study was to evaluate the frequencies of PD-1-positive and PD-ligand 1 (PD-L1)-positive T and B lymphocytes in patients with NPGN and PGN in relation to clinical parameters for the first time...
August 2, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28747914/extrinsic-protein-tyrosine-phosphatase-non-receptor-22-signals-contribute-to-cd8-t-cell-exhaustion-and-promote-persistence-of-chronic-lymphocytic-choriomeningitis-virus-infection
#14
Tatiana Jofra, Giuseppe Galvani, Mirela Kuka, Roberta Di Fonte, Bechara G Mfarrej, Matteo Iannacone, Shahram Salek-Ardakani, Manuela Battaglia, Georgia Fousteri
A genetic variant of the protein tyrosine phosphatase non-receptor 22 (PTPN22) is associated with a wide range of autoimmune diseases; however, the reasons behind its prevalence in the general population remain not completely understood. Recent evidence highlights an important role of autoimmune susceptibility genetic variants in conferring resistance against certain pathogens. In this study, we examined the role of PTPN22 in persistent infection in mice lacking PTPN22 infected with lymphocytic choriomeningitis virus clone 13...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28736431/combined-blockade-of-t-cell-immunoglobulin-and-mucin-domain-3-and-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-results-in-durable-therapeutic-efficacy-in-mice-with-intracranial-gliomas
#15
Jinhu Li, Xiaodong Liu, Yijun Duan, Yueting Liu, Hongqin Wang, Shizhong Lian, Guotao Zhuang, Yimin Fan
BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1...
July 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28733529/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#16
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732506/new-insights-into-blimp-1-in-t-lymphocytes-a-divergent-regulator-of-cell-destiny-and-effector-function
#17
REVIEW
Shin-Huei Fu, Li-Tzu Yeh, Chin-Chen Chu, B Lin-Ju Yen, Huey-Kang Sytwu
B lymphocyte-induced maturation protein-1 (Blimp-1) serves as a master regulator of the development and function of antibody-producing B cells. Given that its function in T lymphocytes has been identified within the past decade, we review recent findings with emphasis on its role in coordinated control of gene expression during the development, differentiation, and function of T cells. Expression of Blimp-1 is mainly confined to activated T cells and is essential for the production of interleukin (IL)-10 by a subset of forkhead box (Fox)p3(+) regulatory T cells with an effector phenotype...
July 21, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28731314/desensitization-to-chemical-and-food-sensitivities-by-low-dose-immunotherapy-ascertained-by-provocation-neutralization-is-associated-with-reduced-influx-of-calcium-ions-into-lymphocytes
#18
Basant K Puri, John McLaren Howard, Jean A Monro
Background Food and chemical sensitivities have detrimental effects on health and the quality of life. The natural course of such sensitivities can potentially be altered through various types of allergen-specific immunotherapy, including low-dose immunotherapy. The molecular mechanism by which low-dose immunotherapy causes desensitization has not thus far been elucidated. While resting lymphocytes maintain a low cytosolic calcium ion concentration, antigen receptor signaling results in calcium ion influx, predominantly via store-operated calcium channels...
April 26, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28724802/partially-exhausted-tumor-infiltrating-lymphocytes-predict-response-to-combination-immunotherapy
#19
Kimberly Loo, Katy K Tsai, Kelly Mahuron, Jacqueline Liu, Mariela L Pauli, Priscila M Sandoval, Adi Nosrati, James Lee, Lawrence Chen, Jimmy Hwang, Lauren S Levine, Matthew F Krummel, Alain P Algazi, Michael D Alvarado, Michael D Rosenblum, Adil I Daud
BACKGROUND: Programmed death 1 (PD-1) inhibition activates partially exhausted cytotoxic T lymphocytes (peCTLs) and induces tumor regression. We previously showed that the peCTL fraction predicts response to anti-PD-1 monotherapy. Here, we sought to correlate peCTL and regulatory T lymphocyte (Treg) levels with response to combination immunotherapy, and with demographic/disease characteristics, in metastatic melanoma patients. METHODS: Pretreatment melanoma samples underwent multiparameter flow cytometric analysis...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28715493/host-genetics-play-a-critical-role-in-controlling-cd8-t-cell-function-and-lethal-immunopathology-during-chronic-viral-infection
#20
Allison F Christiaansen, Megan E Schmidt, Stacey M Hartwig, Steven M Varga
Effective CD8 T cell responses are vital for the control of chronic viral infections. Many factors of the host immune response contribute to the maintenance of effector CD8 T cell responses versus CD8 T cell exhaustion during chronic infection. Specific MHC alleles and the degree of MHC heterogeneity are associated with enhanced CD8 T cell function and viral control during human chronic infection. However, it is currently unclear to what extent host genetics influences the establishment of chronic viral infection...
July 2017: PLoS Pathogens
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