scholarly journals Soluble Human Leukocyte Antigen-G and Its Insertion/Deletion Polymorphism in Papillary Thyroid Carcinoma: Novel Potential Biomarkers of Disease?

2012 ◽  
Vol 97 (11) ◽  
pp. 4080-4086 ◽  
Author(s):  
A. Dardano ◽  
R. Rizzo ◽  
A. Polini ◽  
M. Stignani ◽  
S. Tognini ◽  
...  
Author(s):  
Yanqing Liu ◽  
Meimei Lai ◽  
Yunyan Lou ◽  
Qiuyue Han ◽  
Qing Yang ◽  
...  

Background Nephrotic syndrome is related to immune system dysfunction. Soluble human leukocyte antigen-G has been suggested to have an immunomodulatory role. Additionally, human leukocyte antigen-G expression may be influenced by the 14-base pair insertion/deletion polymorphism. However, this molecule has not been investigated in nephrotic syndrome. Methods Fifty-five children with nephrotic syndrome were enrolled: 24 primary nephrotic syndrome patients and 31 recurrent nephrotic syndrome patients. A group of 120 healthy subjects were included as reference controls. Additionally, 22 patients in nephrotic syndrome remission after treatments were also included. Both nephrotic syndrome patients and healthy subjects were genotyped for the 14-base pair insertion/deletion polymorphism. Plasma soluble human leukocyte antigen-G concentrations and serum immunoglobulin concentrations were determined. Results Nephrotic syndrome patients showed significantly higher levels of both soluble human leukocyte antigen-G and immunoglobulin E compared to normal controls. Nephrotic syndrome patients presented a higher frequency of the −14-base pair allele than did normal controls. Soluble human leukocyte antigen-G concentrations in remission patients were dramatically lower compared to in nephrotic syndrome patients. Moreover, soluble human leukocyte antigen-G and immunoglobulin E were moderately correlated in nephrotic syndrome patients. Conclusions The present study demonstrated that plasma soluble human leukocyte antigen-G concentrations were significantly elevated and that a relationship between serum total immunoglobulin E in nephrotic syndrome patients and the human leukocyte antigen-G −14-base pair allele may be a risk factor for nephrotic syndrome. These findings suggest that soluble human leukocyte antigen-G may be used as a monitoring marker for nephrotic syndrome patients' condition.


2008 ◽  
Vol 69 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Silvia Rosado ◽  
Gema Perez-Chacon ◽  
Susana Mellor-Pita ◽  
Inmaculada Sanchez-Vegazo ◽  
Carmen Bellas-Menendez ◽  
...  

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Roberta Rizzo ◽  
Maria D’Accolti ◽  
Daria Bortolotti ◽  
Francesca Caccuri ◽  
Arnaldo Caruso ◽  
...  

2021 ◽  
Vol 9 (10) ◽  
pp. e003050
Author(s):  
Chia-Ing Jan ◽  
Shi-Wei Huang ◽  
Peter Canoll ◽  
Jeffrey N Bruce ◽  
Yu-Chuan Lin ◽  
...  

BackgroundImmunotherapy against solid tumors has long been hampered by the development of immunosuppressive tumor microenvironment, and the lack of a specific tumor-associated antigen that could be targeted in different kinds of solid tumors. Human leukocyte antigen G (HLA-G) is an immune checkpoint protein (ICP) that is neoexpressed in most tumor cells as a way to evade immune attack and has been recently demonstrated as a useful target for chimeric antigen receptor (CAR)-T therapy of leukemia by in vitro studies. Here, we design and test for targeting HLA-G in solid tumors using a CAR strategy.MethodsWe developed a novel CAR strategy using natural killer (NK) cell as effector cells, featuring enhanced cytolytic effect via DAP12-based intracellular signal amplification. A single-chain variable fragment (scFv) against HLA-G is designed as the targeting moiety, and the construct is tested both in vitro and in vivo on four different solid tumor models. We also evaluated the synergy of this anti-HLA-G CAR-NK strategy with low-dose chemotherapy as combination therapy.ResultsHLA-G CAR-transduced NK cells present effective cytolysis of breast, brain, pancreatic, and ovarian cancer cells in vitro, as well as reduced xenograft tumor growth with extended median survival in orthotopic mouse models. In tumor coculture assays, the anti-HLA-G scFv moiety promotes Syk/Zap70 activation of NK cells, suggesting reversal of the HLA-G-mediated immunosuppression and hence restoration of native NK cytolytic functions. Tumor expression of HLA-G can be further induced using low-dose chemotherapy, which when combined with anti-HLA-G CAR-NK results in extensive tumor ablation both in vitro and in vivo. This upregulation of tumor HLA-G involves inhibition of DNMT1 and demethylation of transporter associated with antigen processing 1 promoter.ConclusionsOur novel CAR-NK strategy exploits the dual nature of HLA-G as both a tumor-associated neoantigen and an ICP to counteract tumor spread. Further ablation of tumors can be boosted when combined with administration of chemotherapeutic agents in clinical use. The readiness of this novel strategy envisions a wide applicability in treating solid tumors.


2013 ◽  
Vol 74 (3) ◽  
pp. 318-324 ◽  
Author(s):  
R.M. Blanco-García ◽  
M.R. López-Álvarez ◽  
I.P. Garrido ◽  
G. Salgado-Cecilia ◽  
J.A. Campillo ◽  
...  

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