CONICET | Buscador de Institutos y Recursos Humanos

In the present study we aim to associate phenotypic deregulation found in BC patients with abnormal NK cells activities. We used our previously established model of Natural Killer (NK) cells an based immunotherapy, focusing on the immune activity triggered by the monoclonal antibody (Ab) Cetuximab against triple negative breast cancer (TNBC) cells. We compared the expression of 13 activating/inhibitory receptors of BC peripheral blood NK cells with those from normal female donors (ND) by flow cytometry. For functional experiments, PBMC were isolated and assayed against different tumor targets including TNBC cells coated with Cetuximab for Ab-dependent cellular cytotoxicity (ADCC) assessment. Advanced BC patients? peripheral blood NK cells display diminished levels of ADCC compared to those from ND (p<0.05). Levels of ADCC, but not of basal lysis, correlated positively with the expression of CD16 receptor in ND (p<0.05). However, this correlation was lost in the BC group, in which a positive correlation was found with DNAM-1, and a negative trend with CD85j. Interestingly, CD85j was upregulated in comparison to ND (p<0.001). We also found a positive linear trend for CD85j expression and histologic tumor grade (p<0.0001), although its overexpression can be found in patients of any clinical stage. We conclude that the overexpression of the inhibitory receptor CD85j may be one possible immunosuppression mechanism in BC and a potential target for immunotherapeutical blockade in order to augment NK cell anti-tumor activity. These results open the possibility of testing a combination of Cetuximab with modulators of the immune response as an attractive therapeutic approach to increase the clinical efficacy of cetuximab in TNBC.