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

Luca Laurenti, Roberta Rizzo, Valentina Audrito, Paola Vacca, Davide Rossi, Davide Brusa, Marina Stignani, Daria Bortolotti, Giovanni D'Arena, Marta Coscia, Francesco Forconi, Gianluca Gaidano, Maria Cristina Mingari, Lorenzo Moretta, Fabio Malavasi, Silvia Deaglio

Risultato della ricerca: Contributo in rivistaArticolo in rivista

30 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)888-896
Numero di pagine9
RivistaHaematologica
DOI
Stato di pubblicazionePubblicato - 2014

Keywords

  • Chronic Lymphocytic Leukemia
  • HLA-G
  • NK cells
  • single nucleotide polymorphism
  • tumor immunology

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