10.3389/fimmu.2018.00926.s001
Alessandra Zingoni
Alessandra
Zingoni
Elisabetta Vulpis
Elisabetta
Vulpis
Francesca Cecere
Francesca
Cecere
Maria G. Amendola
Maria G.
Amendola
Daniel Fuerst
Daniel
Fuerst
Taron Saribekyan
Taron
Saribekyan
Adnane Achour
Adnane
Achour
Tatyana Sandalova
Tatyana
Sandalova
Ilaria Nardone
Ilaria
Nardone
Agnese Peri
Agnese
Peri
Alessandra Soriani
Alessandra
Soriani
Cinzia Fionda
Cinzia
Fionda
Elena Mariggiò
Elena
Mariggiò
Maria T. Petrucci
Maria T.
Petrucci
Maria R. Ricciardi
Maria R.
Ricciardi
Joannis Mytilineos
Joannis
Mytilineos
Marco Cippitelli
Marco
Cippitelli
Cristina Cerboni
Cristina
Cerboni
Angela Santoni
Angela
Santoni
Image_1_MICA-129 Dimorphism and Soluble MICA Are Associated With the Progression of Multiple Myeloma.PDF
Frontiers
2018
multiple myeloma
natural killer cells
NKG2D receptor
MICA polymorphism
predictive biomarker
2018-05-01 04:10:21
Figure
https://frontiersin.figshare.com/articles/figure/Image_1_MICA-129_Dimorphism_and_Soluble_MICA_Are_Associated_With_the_Progression_of_Multiple_Myeloma_PDF/6203720
<p>Natural killer (NK) cells are immune innate effectors playing a pivotal role in the immunosurveillance of multiple myeloma (MM) since they are able to directly recognize and kill MM cells. In this regard, among activating receptors expressed by NK cells, NKG2D represents an important receptor for the recognition of MM cells, being its ligands expressed by tumor cells, and being able to trigger NK cell cytotoxicity. The MHC class I-related molecule A (MICA) is one of the NKG2D ligands; it is encoded by highly polymorphic genes and exists as membrane-bound and soluble isoforms. Soluble MICA (sMICA) is overexpressed in the serum of MM patients, and its levels correlate with tumor progression. Interestingly, a methionine (Met) to valine (Val) substitution at position 129 of the α2 heavy chain domain classifies the MICA alleles into strong (MICA-129Met) and weak (MICA-129Val) binders to NKG2D receptor. We addressed whether the genetic polymorphisms in the MICA-129 alleles could affect MICA release during MM progression. The frequencies of Val/Val, Val/Met, and Met/Met MICA-129 genotypes in a cohort of 137 MM patients were 36, 43, and 22%, respectively. Interestingly, patients characterized by a Val/Val genotype exhibited the highest levels of sMICA in the sera. In addition, analysis of the frequencies of MICA-129 genotypes among different MM disease states revealed that Val/Val patients had a significant higher frequency of relapse. Interestingly, NKG2D was downmodulated in NK cells derived from MICA-129Met/Met MM patients. Results obtained by structural modeling analysis suggested that the Met to Val dimorphism could affect the capacity of MICA to form an optimal template for NKG2D recognition. In conclusion, our findings indicate that the MICA-129Val/Val variant is associated with significantly higher levels of sMICA and the progression of MM, strongly suggesting that the usage of soluble MICA as prognostic marker has to be definitely combined with the patient MICA genotype.</p>