This work investigates the possibility that HLA-G, a molecule modulating innate and adaptive immunity, is part of an immune escape strategy of chronic lymphocytic leukemia cells. A 14 base pair insertion/deletion polymorphism (rs66554220) in the 3'-untranslated region of HLA-G influences mRNA stability and protein expression. The analysis of a cohort of CLL patients confirms that del/del individuals are characterized by higher levels of surface and soluble HLA-G than those of the other two genotypes. In line with its role in immunomodulation, the percentage of regulatory T lymphocytes is higher in del/del patients than in patients with the other genotypes and correlates with the amounts of surface or soluble HLA-G. Furthermore, addition of sHLA-G-rich plasma from CLL patients induces NK cell apoptosis and impairs NK cell lysis, with effects proportional to the amount of soluble HLA-G added. Lastly, the presence of HLA-G 14 bp polymorphism is of prognostic value, with del/del patients showing reduced overall survival, as compared to the other genotypes. These results suggest that i) the HLA-G 14 bp polymorphism influences the levels of surface and soluble HLA-G expression, and that ii) the over-expression of HLA-G molecules contributes to create tolerogenic conditions.

HLA-G is a component of the CLL escape repertoire to generate immune suppression: impact of HLA-G 14 bp (rs66554220) polymorphism

AUDRITO, VALENTINA;BRUSA, Davide;COSCIA, Marta;MALAVASI, Fabio;DEAGLIO, Silvia
2014

Abstract

This work investigates the possibility that HLA-G, a molecule modulating innate and adaptive immunity, is part of an immune escape strategy of chronic lymphocytic leukemia cells. A 14 base pair insertion/deletion polymorphism (rs66554220) in the 3'-untranslated region of HLA-G influences mRNA stability and protein expression. The analysis of a cohort of CLL patients confirms that del/del individuals are characterized by higher levels of surface and soluble HLA-G than those of the other two genotypes. In line with its role in immunomodulation, the percentage of regulatory T lymphocytes is higher in del/del patients than in patients with the other genotypes and correlates with the amounts of surface or soluble HLA-G. Furthermore, addition of sHLA-G-rich plasma from CLL patients induces NK cell apoptosis and impairs NK cell lysis, with effects proportional to the amount of soluble HLA-G added. Lastly, the presence of HLA-G 14 bp polymorphism is of prognostic value, with del/del patients showing reduced overall survival, as compared to the other genotypes. These results suggest that i) the HLA-G 14 bp polymorphism influences the levels of surface and soluble HLA-G expression, and that ii) the over-expression of HLA-G molecules contributes to create tolerogenic conditions.
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http://www.haematologica.org/content/early/2013/12/19/haematol.2013.095281.long
Chronic Lymphocytic Leukemia; HLA-G; NK cells; single nucleotide polymorphism; tumor immunology
R. Rizzo;V. Audrito;P. Vacca;D. Rossi;D. Brusa;M. Stignani;D. Bortolotti;G. D' Arena;M. Coscia;L. Laurenti;F. Forconi;G. Gaidano;M. C. Mingari;L. Moretta;F. Malavasi;S. Deaglio
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/144702
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