MICA-129 Dimorphism and Soluble MICA Are Associated With the Progression of Multiple Myeloma

Frontiers in Immunology
Alessandra ZingoniAngela Santoni

Abstract

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...Continue Reading

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Citations

May 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Maria Teresa BilottaMarco Cippitelli
Jan 18, 2020·Journal of Clinical Medicine·Cinzia FiondaAngela Santoni
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Apr 10, 2020·Frontiers in Immunology·Alessandra ZingoniAngela Santoni
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Aug 17, 2021·Frontiers in Immunology·Mercedes Beatriz FuertesNorberto Walter Zwirner

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Datasets Mentioned

BETA
KP262025

Methods Mentioned

BETA
enzyme-linked immunosorbent assay
FACS
genotyping
ELISA

Software Mentioned

FlowJo
Coot
TreeStar
PyMol Molecular Graphics System
PyMol

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