Artículo
Overexpression of CD85j in TNBC patients inhibits Cetuximab-mediated NK-cell ADCC but can be restored with CD85j functional blockade
Roberti, María Paula; Juliá, Estefanía Paula
; Rocca, Yamila
; Amat, Mora; Bravo, Alicia Inés; Loza, José; Coló, Federico; Loza, Carlos Martín; Fabiano, Verónica; Maino, Merecedes; Podhorzer, Ariel
; Fainboim, Leonardo
; Barrio, Maria Marcela
; Mordoh, Jose
; Levy, Estrella Mariel
Fecha de publicación:
02/2015
Editorial:
Wiley VCH Verlag
Revista:
European Journal of Immunology
ISSN:
0014-2980
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Clinical studies suggest that triple negative breast cancer (TNBC) patients with epidermal growth factor receptor (EGFR)-expressing tumors could benefit from therapy with Cetuximab, which targets EGFR. NK cells are the primary effectors of antibody (Ab)-dependent cell-mediated cytotoxicity (ADCC) and thus play a role in Ab-based therapies. We have previously described diminished levels of Cetuximab-mediated ADCC in vitro in patients with advanced breast cancer. Here, we investigated the potential causes of this NK-cell functional deficiency. We characterized NK-cell activating/inhibitory receptors in the peripheral blood of breast cancer patients and found CD85j inhibitory receptor overexpression. The capacity of NK cells to perform Cetuximab-triggered ADCC against TNBC cells correlated inversely with CD85j expression, even in the presence of the stimulatory cytokines IL-2 or IL-15. Hence, patients expressing high levels of CD85j had an impaired ability to lyse TNBC cells in the presence of Cetuximab. We also found that CD85j overexpression was associated with HLA-I and soluble HLA-G expression by tumors. A CD85j functional blockade with a CD85j antagonist Ab restored ADCC levels in breast cancer patients and reverted this negative effect. Our data suggest that strategies that overcome the hurdles of immune activation could improve Cetuximab clinical efficacy.
Palabras clave:
ADCC
,
CD85J
,
CETUXIMAB
,
EGFR
,
NK CELLS
,
TRIPLE NEGATIVE BREAST CANCER
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Articulos(IIBBA)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Roberti, María Paula; Juliá, Estefanía Paula; Rocca, Yamila; Amat, Mora; Bravo, Alicia Inés; et al.; Overexpression of CD85j in TNBC patients inhibits Cetuximab-mediated NK-cell ADCC but can be restored with CD85j functional blockade; Wiley VCH Verlag; European Journal of Immunology; 45; 5; 2-2015; 1560-1569
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