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https://www.readbyqxmd.com/read/28708863/negative-modulation-of-suppressive-hiv-specific-regulatory-t-cells-by-il-2-adjuvanted-therapeutic-vaccine
#1
Vedran Brezar, Lylia Hani, Mathieu Surenaud, Audrey Hubert, Christine Lacabaratz, Jean-Daniel Lelièvre, Yves Levy, Nabila Seddiki
The potential benefit in using IL-2 in immunotherapy for cancer and autoimmunity has been linked to the modulation of immune responses, which partly relies on a direct effect on Tregs populations. Here, we revisited the role of IL-2 in HIV infection and investigated whether its use as an adjuvant with therapeutic vaccination, impacts on HIV-specific responses. Antiretroviral therapy treated-patients were randomized to receive 4 boosts of vaccination (ALVACHIV/Lipo-6T, weeks 0/4/8/12) followed by 3 cycles of IL-2 (weeks 16/24/32) before treatment interruption (TI) at week40...
July 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28690614/what-else-can-cd39-tell-us
#2
REVIEW
Hai Zhao, Cong Bo, Yan Kang, Hong Li
As the rate-limiting enzyme in ATP/ADP-AMP-adenosine pathway, CD39 would be a novel checkpoint inhibitor target in preventing adenosine-triggered immune-suppressive effect. In addition, CD39(hi) Tregs, but not CD25(hi) Tregs, exhibit sustained Foxp3 levels and functional abilities, indicating it could represent a new specific marker of Tregs. Similarly, inhibition of CD39 enzymatic function at the surface of tumor cells alleviates their immunosuppressive activity. Far from conclusive, present research revealed that CD39 also dephosphorylated and thus inactivated self- and pathogen-associated phosphoantigens of Vγ9Vδ2 T cells, which may be the most promising subpopulation for cellular vaccine...
2017: Frontiers in Immunology
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
#3
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
https://www.readbyqxmd.com/read/28680754/cd39-cd73-upregulation-on-myeloid-derived-suppressor-cells-via-tgf-%C3%AE-mtor-hif-1-signaling-in-patients-with-non-small-cell-lung-cancer
#4
Jieyao Li, Liping Wang, Xinfeng Chen, Lifeng Li, Yu Li, Yu Ping, Lan Huang, Dongli Yue, Zhen Zhang, Fei Wang, Feng Li, Li Yang, Jianmin Huang, Shuangning Yang, Hong Li, Xuan Zhao, Wenjie Dong, Yan Yan, Song Zhao, Bo Huang, Bin Zhang, Yi Zhang
CD39/CD73-adenosine pathway has been recently defined as an important tumor-induced immunosuppressive mechanism. We here documented a fraction of CD11b(+)CD33(+) myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor tissues from non-small cell lung cancer (NSCLC) patients expressed surface ectonucleotidases CD39 and CD73. Tumor TGF-β stimulated CD39 and CD73 expression, thereby inhibited T cell and NK cell activity, and protected tumor cells from the cytotoxic effect of chemotherapy through ectonucleotidase activity...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679740/role-of-adp-receptors-on-platelets-in-the-growth-of-ovarian-cancer
#5
Min Soon Cho, Kyunghee Noh, Monika Haemmerle, Dan Li, Hyun Park, Qianghua Hu, Takeshi Hisamatsu, Takashi Mitamura, Sze Ling Celia Mak, Satya Kunapuli, Qing Ma, Anil K Sood, Vahid Afshar-Kharghan
We investigated the effect of platelets on ovarian cancer, and role of ADP receptors (P2Y12 and P2Y1) on platelets in the growth of primary ovarian cancer tumors. We showed that in murine models of ovarian cancer, P2Y12 inhibitor (Ticagrelor) reduced tumor growth by 60% compared to aspirin and 75% compared to placebo. In P2Y12(-/-) mice, the growth of syngeneic ovarian cancer tumors was reduced by >85% compared to WT mice. On the other hand, there was no difference in the tumor growth between P2Y1(-/-) and WT mice...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28674498/nimotuzumab-induces-nk-cell-activation-cytotoxicity-dendritic-cell-maturation-and-expansion-of-egfr-specific-t-cells-in-head-and-neck-cancer-patients
#6
Zaima Mazorra, Anabel Lavastida, Fernando Concha-Benavente, Anet Valdés, Raghvendra M Srivastava, Tatiana M García-Bates, Esperanza Hechavarría, Zuyen González, Amnely González, Martha Lugiollo, Iván Cuevas, Carlos Frómeta, Braulio F Mestre, Maria C Barroso, Tania Crombet, Robert L Ferris
Survival benefit and long-term duration of clinical response have been seen using the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody (mAb) nimotuzumab. Blocking EGFR signaling may not be the only mechanism of action underlying its efficacy. As an IgG1 isotype mAb, nimotuzumab's capacity of killing tumor cells by antibody dependent cellular cytotoxicity (ADCC) and to induce an immune response in cancer patients have not been studied. ADCC-induced by nimotuzumab was determined using a (51)Cr release assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28658673/hyperthermia-and-associated-changes-in-membrane-fluidity-potentiate-p2x7-activation-to-promote-tumor-cell-death
#7
Paola de Andrade Mello, Shu Bian, Luiz Eduardo Baggio Savio, Haohai Zhang, Jingping Zhang, Wolfgang Junger, Márcia Rosângela Wink, Guido Lenz, Andréia Buffon, Yan Wu, Simon Christopher Robson
Extracellular ATP (eATP) accumulation within the tumor microenvironment (TME) has the potential to activate purinergic signaling. The eATP evoked signaling effects bolster antitumor immune responses while exerting direct cytotoxicity on tumor cells and vascular endothelial cells, mediated at least in part through P2X7 receptors. Approaches to augment purinergic signaling in TME e.g. by ectonucleotidase CD39 blockade, and/or boosting P2X7 functional responses, might be used as immunomodulatory therapies in cancer treatment...
June 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28658271/regulatory-t-cell-frequencies-and-phenotypes-following-anti-viral-vaccination
#8
A Charlotte M T de Wolf, Susan van Aalst, Irene S Ludwig, Caroline L Bodinham, David J Lewis, Ruurd van der Zee, Willem van Eden, Femke Broere
Regulatory T cells (Treg) function in the prevention of excessive inflammation and maintenance of immunological homeostasis. However, these cells may also interfere with resolution of infections or with immune reactions following vaccination. Effects of Treg on vaccine responses are nowadays investigated, but the impact of vaccination on Treg homeostasis is still largely unknown. This may be a relevant safety aspect, since loss of tolerance through reduced Treg may trigger autoimmunity. In exploratory clinical trials, healthy adults were vaccinated with an influenza subunit vaccine plus or minus the adjuvant MF59®, an adjuvanted hepatitis B subunit vaccine or a live attenuated yellow fever vaccine...
2017: PloS One
https://www.readbyqxmd.com/read/28617999/adenosine-an-endogenous-mediator-in-the-pathogenesis-of-gynecological-cancer
#9
REVIEW
Amirhossein Bahreyni, Seyed Sattar Samani, Elnaz Ghorbani, Farzad Rahmani, Reza Khayami, Younes Toroghian, Reihane Behnam-Rassouli, Majid Khazaei, Mikhail Ryzhikov, Mohammad Reza Parizadeh, Malihe Hasanzadeh, Amir Avan, Seyed Mahdi Hassanian
Extracellular concentration of adenosine increases in the hypoxic tumor microenvironment. Adenosine signaling regulates apoptosis, angiogenesis, metastasis and immune suppression in cancer cells. Adenosine-induced cell responses depend upon different subtypes of adenosine receptors activation and type of cancer. Suppression of adenosine signaling via inhibition of adenosine receptors or adenosine generating enzymes including CD39 and CD73 on ovarian or cervical cancer cells is a potentially novel therapeutic approach for gynecological cancer patients...
June 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28603527/intratumoral-foxp3-helios-regulatory-t-cells-upregulating-immunosuppressive-molecules-are-expanded-in-human-colorectal-cancer
#10
Azharuddin Sajid Syed Khaja, Salman M Toor, Haytham El Salhat, Bassam R Ali, Eyad Elkord
Regulatory T cells (Tregs) can be antitumorigenic or pro-tumorigenic in colorectal cancer (CRC) depending on the presence of different Treg subsets with various immunosuppressive molecules. Some studies reported the phenotypic characteristics of tumor-infiltrating immune cells in CRC, but limited studies have focused on the co-expression of suppressive molecules on immune cells. The aim of this study was to characterize immune cells in the tumor microenvironment (TME), compared to paired adjacent non-tumor colon tissue of CRC patients...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28578124/influence-of-photodynamic-therapy-on-peripheral-immune-cell-populations-and-cytokine-concentrations-in-head-and-neck-cancer
#11
M N Theodoraki, K Lorenz, R Lotfi, D Fürst, C Tsamadou, S Jaekle, J Mytilineos, C Brunner, J Theodorakis, T K Hoffmann, S Laban, P J Schuler
BACKGROUND: Photodynamic therapy (PDT) represents a palliative treatment option for a selected group of patients with head and neck squamous cell carcinoma (HNSCC). PDT induces a local inflammatory reaction with the potential to initiate antitumor immune responses. However, the systemic impact on peripheral immune cells has not been described so far. METHODS: HNSCC patients (n=9) were treated with PDT in a palliative setting. All patients had previously undergone several oncologic treatment regimens...
May 31, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28574843/characterization-of-tumor-associated-t-lymphocyte-subsets-and-immune-checkpoint-molecules-in-head-and-neck-squamous-cell-carcinoma
#12
Axel Lechner, Hans Schlößer, Sacha I Rothschild, Martin Thelen, Sabrina Reuter, Peter Zentis, Alexander Shimabukuro-Vornhagen, Sebastian Theurich, Kerstin Wennhold, Maria Garcia-Marquez, Lars Tharun, Alexander Quaas, Astrid Schauss, Jörg Isensee, Tim Hucho, Christian Huebbers, Michael von Bergwelt-Baildon, Dirk Beutner
The composition of tumor-infiltrating lymphocytes (TIL) reflects biology and immunogenicity of cancer. Here, we characterize T-cell subsets and expression of immune checkpoint molecules in head and neck squamous cell carcinoma (HNSCC). We analyzed TIL subsets in primary tumors (n = 34), blood (peripheral blood mononuclear cells (PBMC); n = 34) and non-cancerous mucosa (n = 7) of 34 treatment-naïve HNSCC patients and PBMC of 15 healthy controls. Flow cytometry analyses revealed a highly variable T-cell infiltration mainly of an effector memory phenotype (CD45RA-/CCR7-)...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28554875/cd39-limits-p2x7-receptor-inflammatory-signaling-and-attenuates-sepsis-induced-liver-injury
#13
Luiz Eduardo Baggio Savio, Paola de Andrade Mello, Vanessa R Figliuolo, Thiago F de Avelar Almeida, Patrícia T Santana, Suellen D S Oliveira, Claudia L M Silva, Linda Feldbrügge, Eva Csizmadia, Richard D Minshall, Maria Serena Longhi, Yan Wu, Simon C Robson, Robson Coutinho-Silva
BACKGROUND & AIMS: The severity of sepsis can be linked to excessive inflammatory responses resulting in hepatic injury with progressive cholestasis. Monocyte/macrophages have been linked to the pathogenesis of cholestasis, cellular injury, and liver failure. P2X7 receptor activation by extracellular ATP (eATP) exacerbates inflammation by augmenting cytokine production; while CD39 scavenges eATP to generate adenosine, thereby limiting P2X7 activation and resulting in A2A receptor stimulation...
May 26, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28547381/purinergic-signalling-links-mechanical-breath-profile-and-alveolar-mechanics-with-the-pro-inflammatory-innate-immune-response-causing-ventilation-induced-lung-injury
#14
REVIEW
Djo Hasan, Paul Blankman, Gary F Nieman
Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine. Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells...
May 26, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28547076/purinergic-signaling-during-intestinal-inflammation
#15
REVIEW
Maria Serena Longhi, Alan Moss, Zhenghui Gordon Jiang, Simon C Robson
Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer...
May 26, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28536578/expansion-of-cd25-negative-forkhead-box-p3-positive-t-cells-during-hiv-and-mycobacterium-tuberculosis-infection
#16
Matías T Angerami, Guadalupe V Suarez, María B Vecchione, Natalia Laufer, Diego Ameri, Graciela Ben, Hector Perez, Omar Sued, Horacio Salomón, María F Quiroga
Tuberculosis (TB) and HIV alter the immune system, and coinfected (HIV-TB) individuals usually present deregulations of T-lymphocytic immune response. We previously observed an increased frequency of "unconventional" CD4(+)CD25(-)FoxP3(+) Treg (uTreg) population during HIV-TB disease. Therefore, we aimed to explore the phenotype and function of uTreg and conventional CD4(+)CD25(+)FoxP3(+) Treg subsets (cTreg) in this context. We evaluated the expression of CD39, programmed cell death protein 1 (PD1), glucocorticoid-induced tumor necrosis factor receptor (GITR), and the effector/memory distribution by flow cytometry in cTreg and uTreg...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28533380/ccr8-foxp3-treg-cells-as-master-drivers-of-immune-regulation
#17
Yiftah Barsheshet, Gizi Wildbaum, Eran Levy, Alon Vitenshtein, Chika Akinseye, Jeremy Griggs, Sergio A Lira, Nathan Karin
The current study identifies CCR8(+) regulatory T cells (Treg cells) as drivers of immunosuppression. We show that in human peripheral blood cells, more than 30% of Treg up-regulate CCR8 following activation in the presence of CCL1. This interaction induces STAT3-dependent up-regulation of FOXp3, CD39, IL-10, and granzyme B, resulting in enhanced suppressive activity of these cells. Of the four human CCR8 ligands, CCL1 is unique in potentiating Treg cells. The relevance of these observations has been extended using an experimental model of multiple sclerosis [experimental autoimmune encephalomyelitis, (EAE)] and a stabilized version of mouse CCL1 (CCL1-Ig)...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28529533/low-expression-of-cd39-and-cd73-genes-in-centenarians-compared-with-octogenarians
#18
Almudena Crooke, Juan Martínez-Henández, Joaquín Martínez-López, Alfonso Cruz-Jentoft, Fernando Huete-Toral, Jesús Pintor
Ageing involves a progressive decline of the body's regulatory systems including immune system. Adenosine regulates immune function by interaction with its receptors, mainly adenosine A2A receptor, present on the surface of immune cells. Furthermore, cellular response to this nucleoside is highly dependent on its extracellular concentration that is regulated by ecto-enzymes such as CD39 and CD73. Therefore, the aim of this study was to investigate the effect of age on adenosine A2A receptor, CD39 and CD73 gene expression...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#19
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
June 5, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28509416/the-importance-of-cd39-cd43-cd81-and-cd95-expression-for-differentiating-b-cell-lymphoma-by-flow-cytometry
#20
Chandra Chiappin Cardoso, Mariangeles Auat, Iris Mattos Santos-Pirath, Renata Cristina Messores Rudolf-Oliveira, Jessica Pires da Silva, Bárbara Gil Lange, Danielle Siegel, Ana Carolina Rabello de Moraes, Joanita Angela Gonzaga Del Moral, Maria Claudia Santos-Silva
BACKGROUND: B cell lymphomas' (BCL) current diagnosis is usually based on a combination of morphology, immunophenotype, recurrent cytogenetic aberration and clinical features. However, even with these diagnostic tools, a definitive diagnosis can be difficult to achieve. Therefore, the aim of this study was to assess the profile of CD39, CD43, CD81, and CD95 expressions in diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and Burkitt lymphoma (BL) cases. METHODS: To address this issue, we investigated the expression of CD39, CD43, CD81, and CD95 by eight-color flow cytometry in retrospective cases from 2014 to 2016...
May 16, 2017: Cytometry. Part B, Clinical Cytometry
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