Intracellular retention of the NKG2D ligand MHC Class I chain-related gene A in human melanomas confers immune privilege and prevents NK cell-mediated cytotoxicity
- Fuertes, Mercedes Beatriz
- Girart, Maria Victoria
- Molinero, Luciana Lorena
- Domaica, Carolina Ines
- Rossi, Lucas Ezequiel
- Barrio, Maria Marcela
- Mordoh, Jose
- Rabinovich, Gabriel Adrián
- Zwirner, Norberto Walter
DOIAbstract
Most tumors grow in immunocompetent hosts despite expressing NKG2D ligands (NKG2DLs) such as the MHC class I chain-related genes A and B (MICA/B). However, their participation in tumor cell evasion is still not completely understood. Here we demonstrate that several human melanomas (cell lines and freshly isolated metastases) do not express MICA on the cell surface but have intracellular deposits of this NKG2DL. Susceptibility to NK cell-mediated cytotoxicity correlated with the ratio of NKG2DLs to HLA class I molecules but not with the amounts of MICA on the cell surface of tumor cells. Transfection-mediated overexpression of MICA restored cell surface expression and resulted in an increased in vitro cytotoxicity and IFN-gamma secretion by...
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