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Yahui Ding, Huier Gao, Quan Zhang
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by morphology and chromosome aberrations with high mortality. Leukemia stem cells (LSCs) in AML played important roles in leukemia initiation, progression, and were considered to be the root of chemotherapeutic drug resistance and disease relapse. The identification and targeting LSCs depended on membrane markers like CD34, CD38, CD123, TIM3, CD25, CD32 and CD96. In addition, the transcription factors were also therapeutic targets in eradicating LSCs, such as histone deacetylases (HDACs), NF-κB, HIF-1α and β-catenin...
2017: Stem Cell Investigation
Yongfang Jiang, Ping Xu, Dandan Yao, Xi Chen, Haibin Dai
BACKGROUND Leukemia stem cells (LSC) are involved in the incidence, drug resistance, and relapse of leukemia while LSC-related antigen CD33, CD96, and DAPK expression in AML and its prognosis is still unclear. This study explored LSC-related antigens expression in acute myeloid leukemia (AML) and its prognosis. MATERIAL AND METHODS A total of 156 cases of AML patients were enrolled in the experiment. The expression of CD33, CD96, and DAPK in CD34+CD38-CD123+ LSC were tested by flow cytometry. The survival curve was established using the Kaplan-Meier method...
April 9, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
William C Dougall, Sema Kurtulus, Mark J Smyth, Ana C Anderson
While therapies targeting the co-inhibitory or immune checkpoint receptors PD-1 and CTLA-4 have shown remarkable success in many cancers, not all patients benefit from these therapies. This has catalyzed enormous interest in the targeting of other immune checkpoint receptors. In this regard, TIGIT and CD96 have recently entered the limelight as novel immune checkpoint receptor targets. TIGIT and CD96 together with the co-stimulatory receptor CD226 form a pathway that is analogous to the CD28/CTLA-4 pathway, in which shared ligands and differential receptor:ligand affinities fine-tune the immune response...
March 2017: Immunological Reviews
Maria Carmen Ochoa, Luna Minute, Inmaculada Rodriguez, Saray Garasa, Elisabeth Perez-Ruiz, Susana Inogés, Ignacio Melero, Pedro Berraondo
Antibody-dependent cellular cytotoxicity (ADCC) is a set of mechanisms that target cells coated with IgG antibodies of the proper subclasses (IgG1 in the human) to be the prey of cell-to-cell cytolysis executed by immune cells expressing FcRIIIA (CD16A). These effectors include not only natural killer (NK) cells but also other CD16(+) subsets such as monocyte/macrophages, NKT cells or γδ T cells. In cancer therapy, ADCC is exploited by antibodies that selectively recognize proteins on the surface of malignant cells...
April 2017: Immunology and Cell Biology
Yun-Peng Peng, Chun-Hua Xi, Yi Zhu, Ling-Di Yin, Ji-Shu Wei, Jing-Jing Zhang, Xin-Chun Liu, Song Guo, Yue Fu, Yi Miao
The progression of pancreatic cancer (PC) is significantly associated with tumor immune escape, which may be associated with nature killer (NK) cell dysfunction. CD226, CD96, and TIGIT, which share the ligand CD155, play important roles in the regulation of NK cell function. The present study was conducted to investigate the roles of these molecules in NK cells from PC patients. Expression of these molecules on NK cells was detected from samples of 92 pancreatic cancer patients and 40 healthy controls. The expression of CD155 was also evaluated by immunohistochemistry in 88 pancreatic cancer tissues...
October 11, 2016: Oncotarget
Stephen J Blake, William C Dougall, John J Miles, Michele W L Teng, Mark J Smyth
The receptors CD96 and TIGIT are expressed on the surface of T and natural killer (NK) cells, and recent studies suggest both play important inhibitory roles in immune function. CD96 has been shown to modulate immune cell activity in mice, with Cd96(-)(/)(-) mice displaying hypersensitive NK-cell responses to immune challenge and significant tumor resistance. TIGIT overexpression has been shown to reduce NK-cell-mediated cytotoxicity. TIGIT is also upregulated on T cells during cancer and chronic viral infection, with expression associated with effector T-cell exhaustion and increased regulatory T-cell suppression...
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Tihana Lenac Rovis, Paola Kucan Brlic, Noa Kaynan, Vanda Juranic Lisnic, Ilija Brizic, Stefan Jordan, Adriana Tomic, Daria Kvestak, Marina Babic, Pinchas Tsukerman, Marco Colonna, Ulrich Koszinowski, Martin Messerle, Ofer Mandelboim, Astrid Krmpotic, Stipan Jonjic
The poliovirus receptor (PVR) is a ubiquitously expressed glycoprotein involved in cellular adhesion and immune response. It engages the activating receptor DNAX accessory molecule (DNAM)-1, the inhibitory receptor TIGIT, and the CD96 receptor with both activating and inhibitory functions. Human cytomegalovirus (HCMV) down-regulates PVR expression, but the significance of this viral function in vivo remains unknown. Here, we demonstrate that mouse CMV (MCMV) also down-regulates the surface PVR. The m20.1 protein of MCMV retains PVR in the endoplasmic reticulum and promotes its degradation...
August 22, 2016: Journal of Experimental Medicine
Swati Garg, Kanjaksha Ghosh, Manisha Madkaikar
A putative leukemic stem cell population in AML defined by Lin-/CD38-/CD34+ is associated with disease prognosis. Antigens that are differentially expressed on normal and leukemic stem cells are known for their potential use in AML prognosis, but their differential expression on blast and pLSC has not been extensively explored in the clinical setting. In the present study, we sought to identify expression level differences of CD44, CD90, CD96, CD123, CD25 and intracellular WT-1; on AML blasts and Lin-/CD38-/CD34+ population in CD34+ AMLs using multi-parametric flow cytometry...
May 2016: International Journal of Hematology
Wenwen Yan, Lin Zhou, Siwan Wen, Qianglin Duan, Feifei Huang, Yu Tang, Xiaohong Liu, Yongyan Chai, Lemin Wang
BACKGROUND: To evaluate the activity of natural killer cells through their inhibitory and activating receptors and quantity in peripheral blood mononuclear cells extracted from patients with acute myocardial infarction, stable angina pectoris and the controls. METHODS: 100 patients with myocardial infarction, 100 with stable angina, and 20 healthy volunteers were recruited into the study. 20 randomly chosen people per group were examined for the whole human genome microarray analysis to detect the gene expressions of all 40 inhibitory and activating natural killer cell receptors...
2015: International Journal of Clinical and Experimental Pathology
Stephen J Blake, Kimberley Stannard, Jing Liu, Stacey Allen, Michelle C R Yong, Deepak Mittal, Amelia Roman Aguilera, John J Miles, Viviana P Lutzky, Lucas Ferrari de Andrade, Ludovic Martinet, Marco Colonna, Kazuyoshi Takeda, Florian Kühnel, Engin Gurlevik, Günter Bernhardt, Michele W L Teng, Mark J Smyth
UNLABELLED: CD96 has recently been shown as a negative regulator of mouse natural killer (NK)-cell activity, with Cd96(-/-)mice displaying hyperresponsive NK cells upon immune challenge. In this study, we have demonstrated that blocking CD96 with a monoclonal antibody inhibited experimental metastases in three different tumor models. The antimetastatic activity of anti-CD96 was dependent on NK cells, CD226 (DNAM-1), and IFNγ, but independent of activating Fc receptors. Anti-CD96 was more effective in combination with anti-CTLA-4, anti-PD-1, or doxorubicin chemotherapy...
April 2016: Cancer Discovery
Roser Urreizti, Neus Roca-Ayats, Judith Trepat, Francisco Garcia-Garcia, Alejandro Aleman, Daniela Orteschi, Giuseppe Marangi, Giovanni Neri, John M Opitz, Joaquin Dopazo, Bru Cormand, Lluïsa Vilageliu, Susana Balcells, Daniel Grinberg
Opitz C trigonocephaly (or Opitz C syndrome, OTCS) and Bohring-Opitz syndrome (BOS or C-like syndrome) are two rare genetic disorders with phenotypic overlap. The genetic causes of these diseases are not understood. However, two genes have been associated with OTCS or BOS with dominantly inherited de novo mutations. Whereas CD96 has been related to OTCS (one case) and to BOS (one case), ASXL1 has been related to BOS only (several cases). In this study we analyze CD96 and ASXL1 in a group of 11 affected individuals, including 2 sibs, 10 of them were diagnosed with OTCS, and one had a BOS phenotype...
January 2016: American Journal of Medical Genetics. Part A
Hristo Georgiev, Inga Ravens, Akira Shibuya, Reinhold Förster, Günter Bernhardt
The cell surface receptor CD155 influences a variety of immune processes by binding to its ligands CD226, CD96, or TIGIT. Here, we report that the interaction of CD155 with CD226 in the thymus of BALB/c mice has a dual function. It directly influences the dwell time of memory-like CD8(+) T cells, while it is indirectly involved in generating these cells. It was shown earlier that a massive emergence of memory-like CD8 T cells in thymus crucially depends on abundant IL-4, secreted in steady state by iNKT2 (where iNKT is invariant NKT) cells, a subclass of iNKT cells...
April 2016: European Journal of Immunology
Aurélie Cleret-Buhot, Yuwei Zhang, Delphine Planas, Jean-Philippe Goulet, Patricia Monteiro, Annie Gosselin, Vanessa Sue Wacleche, Cécile L Tremblay, Mohammad-Ali Jenabian, Jean-Pierre Routy, Mohamed El-Far, Nicolas Chomont, Elias K Haddad, Rafick-Pierre Sekaly, Petronela Ancuta
BACKGROUND: The HIV-1 infection is characterized by profound CD4(+) T cell destruction and a marked Th17 dysfunction at the mucosal level. Viral suppressive antiretroviral therapy restores Th1 but not Th17 cells. Although several key HIV dependency factors (HDF) were identified in the past years via genome-wide siRNA screens in cell lines, molecular determinants of HIV permissiveness in primary Th17 cells remain to be elucidated. RESULTS: In an effort to orient Th17-targeted reconstitution strategies, we investigated molecular mechanisms of HIV permissiveness in Th17 cells...
2015: Retrovirology
Wei Zhang, Zonghong Shao, Rong Fu, Huaquan Wang, Lijuan Li, Hui Liu
BACKGROUND: Our goal was to detect the expression of CD96 and CD123 in myelodysplastic syndromes (MDS) and their proliferation and differentiation characteristics. METHODS: Forty-three patients with MDS, thirteen AML patients diagnosed in the Hematology Department of General Hospital of Tianjin Medical University, and sixteen healthy controls were enrolled in this study. The expressions of CD96 and CD123 on CD34+CD38- bone marrow cells (BMC) of these patients and controls were measured by FACS...
2015: Clinical Laboratory
Wen DU, Yanjie Hu, Cong Lu, Juan Li, Wei Liu, Yanli He, Ping Wang, Chen Cheng, Y U Hu, Shiang Huang, Junxia Yao, Jin'e Zheng
Resistance to chemotherapy is a major challenge for leukemia treatment. It has been suggested that leukemia stem cells (LSCs), a small pool of self-renewing leukemic cells, play important roles in development of chemotherapy resistance. The expression of cluster of differentiation 96 (CD96), a potential marker for LSCs, was investigated in CD34(+)CD38(-) cells of 105 acute leukemia (AL) patients by flow cytometry. The data showed that all the CD34(+), CD34(+)CD38(-) and CD34(+)CD38(-)CD96(+) proportions were much higher in AL compared to the normal control (P<0...
July 2015: Molecular and Clinical Oncology
Swati Garg, Chandrakala Shanmukhaiah, Supreet Marathe, Prashant Mishra, Vunditi Babu Rao, Kanjaksha Ghosh, Manisha Madkaikar
Acute myeloid leukemia is often called as stem cell disease that presents with treatment failure and poor disease outcome. Leukemic stem cells in acute myeloid leukemia (AML) are enriched in Lineage-/CD38-/CD34+ compartment of CD34-positive AML. Many markers important for stem cell biology have been reported for their association with leukemic stem cell population, but what remains clinically most important is a rapid identification of prognostic information. In this study, we evaluated four signal transduction pathways and thirteen markers on Lin-/CD38-/CD34+ population in AML...
March 2016: European Journal of Haematology
Georg Gruenbacher, Oliver Nussbaumer, Hubert Gander, Bernhard Steiner, Nicolai Leonhartsberger, Martin Thurnher
The potentially oncogenic mevalonate pathway provides building blocks for protein prenylation and induces cell proliferation and as such is an important therapeutic target. Among mevalonate metabolites, only isopentenyl pyrophosphate (IPP) has been considered to be an immunologically relevant antigen for primate-specific, innate-like Vγ9Vδ2 T cells with antitumor potential. We show here that Vγ9Vδ2 T cells pretreated with the stress-related, inflammasome-dependent cytokine interleukin 18 (IL-18) were potently activated not only by IPP but also by all downstream isoprenoid pyrophosphates that exhibit combined features of antigens and cell-extrinsic metabolic cues...
2014: Oncoimmunology
Ludovic Martinet, Mark J Smyth
Natural killer (NK) cells are innate lymphocytes that are crucial for the control of infections and malignancies. NK cells express a variety of inhibitory and activating receptors that facilitate fine discrimination between damaged and healthy cells. Among them, a family of molecules that bind nectin and nectin-like proteins has recently emerged and has been shown to function as an important regulator of NK cell functions. These molecules include CD226, T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), CD96, and cytotoxic and regulatory T cell molecule (CRTAM)...
April 2015: Nature Reviews. Immunology
Meijun Du, Tiezheng Yuan, Kala F Schilter, Rachel L Dittmar, Alexander Mackinnon, Xiaoyi Huang, Michael Tschannen, Elizabeth Worthey, Howard Jacob, Shu Xia, Jianzhong Gao, Lori Tillmans, Yan Lu, Pengyuan Liu, Stephen N Thibodeau, Liang Wang
Chromosome 8q24 locus contains regulatory variants that modulate genetic risk to various cancers including prostate cancer (PC). However, the biological mechanism underlying this regulation is not well understood. Here, we developed a chromosome conformation capture (3C)-based multi-target sequencing technology and systematically examined three PC risk regions at the 8q24 locus and their potential regulatory targets across human genome in six cell lines. We observed frequent physical contacts of this risk locus with multiple genomic regions, in particular, inter-chromosomal interaction with CD96 at 3q13 and intra-chromosomal interaction with MYC at 8q24...
January 1, 2015: Human Molecular Genetics
Antonieta Chávez-González, Elisa Dorantes-Acosta, Dafne Moreno-Lorenzana, Antonio Alvarado-Moreno, Lourdes Arriaga-Pizano, Héctor Mayani
BACKGROUND AND AIMS: In trying to contribute to our knowledge on the biology of hematopoietic stem cells (HSC) and hematopoietic progenitor cells (HPC) from pediatric acute myeloid leukemia (AML), in the present study we analyzed the expression of four cell surface antigens relevant to human hematopoiesis-CD90, CD96, CD117, and CD123-in bone marrow from pediatric AML patients and normal control subjects. METHODS: CD34(+) CD38(-) cells (enriched for HSC) and CD34(+) CD38(+) cells (enriched for HPC) were resolved on the basis of CD34 and CD38 expression...
May 2014: Archives of Medical Research
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