HLA-I 类表达缺失、肿瘤微环境与乳腺癌预后

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 HIF1 expression and high TIL-density.

Cell line experiments (MCF7 and T47D) showed that induction of HLAs in cancer cells following incubation with lymphocytes or IFN , 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 HIF1 expression may identify subgroups of BCa patients who would benefit from immunotherapy.