HLA-class-I expression loss, tumor microenvironment and breast cancer prognosis

•Extensive loss HLA-class-I expression occurs 76.6% of breast carcinomas.•HLA-preservation is associated with high TIL-density and low HIF1α expression.•Hypoxia suppresses HLA-class-I expression in breast cancer cell lines.•Induction of HLA following incubation with IFNγ is abrogated under hypoxia.•HLA-preservation is linked with better distant metastasis-free survival. Loss of HLA-class-I molecule expression by cancer cells is a frequent event in human tumors that may lead to immune evasion from cytotoxic T-cells. We examined the expression patterns of HLA-class-I molecules in a series of 175 patients with operable breast cancer (BCa). Extensive loss of BCa cell HLA-class-I expression was noted 76.6 % of patients (27.5 % complete loss). A significant association of HLA-preservation with high TIL-density (p = 0.001) was documented. Preservation of HLA was evident only in BCa carcinomas with low HIF1α expression and high TIL-density. Cell line experiments (MCF7 and T47D) showed that induction of HLAs in cancer cells following incubation with lymphocytes or IFNγ, was abrogated under hypoxic conditions. HLA-preservation was linked with better distant metastasis-free survival (p = 0.01), which was confirmed also in multivariate analysis (p = 0.02, HR 3.17). Studying the expression of HLA-class-I molecules in parallel with TIL-density and HIF1α expression may identify subgroups of BCa patients who would benefit from immunotherapy.