Host immunosurveillance contributes to the control of erbB-2 overexpression in HLA-A2-breast-cancer patients

Overexpression of gp185(erbB-2) has been associated with reduced survival in breast-cancer patients. Our earlier results, now confirmed in a larger cohort of patients (798), evidenced that the HLA-A2 allele may participate in the modulation of the erbB-2 tumor phenotype in vivo. In the present study, we evaluated other clinico-biopathologic parameters possibly involved in the host immune response against erbB-2. Localization of the CD3⁺ T-cell infiltrate was taken into consideration in 705 primary breast tumors, and expression of HLA-class-I and HLA-A2 antigens was evaluated in a subgroup of 170 frozen primary tumors of HLA-A2-positive patients. The presence or the absence of HLA-class-I and HLA-A2 antigens in primary tumors did not correlate with erbB-2 expression. However, HLA-A2-positive tumors preferentially showed intratumoral lymphocyte localization, whereas the lesions displaying undetectable HLA-class-I expression showed peritumoral CD3⁺ T-cell localization. Taking into account erbB-2 immunoreactivity, we found that the relationship between HLA-A2 expression and intratumoral CD3⁺ T-lymphocyte localization is significant only in the erbB-2 negative subset, whereas the relationship between lack of HLA-class-I expression and peritumoral CD3⁺ T-lymphocyte localization is significant only in the erbB- 2-positive subset. These data provide novel in vivo evidence of the possible contribution of the host immune system to control of erbB-2 oncogene overexpression in breast cancer.