Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer

Abstract

BackgroundHuman leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear.MethodsWe evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed.ResultsTotal loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II–IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I–positive tumors than in HLA-I–negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort.ConclusionsOur findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.

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“…In breast cancer, these molecules are downregulated in 40-50% of tumor tissues ( 81 ). Their downregulation has been associated with a poor prognosis due to immune-escape mechanism ( 82 , 83 ). Conversely, expression of HLA-A and HLA-B represents favorable prognosis, because it identifies immune-activated tumors ( 84 ).…”

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“…Although the data are conflicting, the majority of studies indicate that HLA-I downregulation is associated with poor prognosis. In a large retrospective study, the correlation of HLA-I expression with clinical outcome was assessed in 465 surgically resected breast cancer specimens including 310 primary HR+ tumors ( 97 ). Complete loss of HLA-I was observed in about 18% of both the HR+ and HR- subsets and survival analysis revealed that HLA-I expression loss was significantly correlated with worse disease-specific survival (DSS).…”