Expression and clinical significance of HLA class I antigen and tumor-infiltrating immune cells in human non-small cell lung cancer Free

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EMR8-5 is a novel monoclonal anti-pan HLA class I heavy chain antibody which detects HLA-A, B, and C antigen in formalin-fixed paraffin embedded tissue. We conducted a retrospective study to assess the correlation between HLA class I expression and clinicopathological factors in human non-small cell lung cancer (NSCLCs) using this antibody.

The expressions of HLA class I antigen and beta-2 microglobulin were assessed in 161 resected primary NSCLCs by standard immunohistochemical staining method, using anti-HLA class I antibody (EMR8-5), anti-beta-2 microglobulin antibody (EMR-b6), anti-CD8 antibody (clone C8/144b), and anti-CD56 antibody (clone 1B6). The expressions of HLA class I and beta-2 microglobulin were classified into three categories; they were defined as positive when tumor cells whose membrane was strongly and homogenously stained at the same level as stromal lymphocytes or endothelial cells were more than 80%, weakly positive when they are between 20 and 80% or tumor cells whose membrane was less weakly stained than stromal lymphocytes or endothelial cells, and negative when stained cells were less than 20%. Cases with weakly positve and negative staining were also defined as the down-regulation group. CD8+ T cells and CD56+ NK cells were counted within cancer nests and cancer stroma.

The expression of HLA class I was positive in 50 tumors (31%), weakly positive in 57 tumors (35%), and negative in 54 tumors (34%). There was a significant correlation between the expressions of HLA class I and beta-2-microglobulin with Cohen's kappa coefficient of 0.71. The down-regulation of HLA class I expression showed a significant correlation with male patients, smoking history, non-adenocarcinoma histology, and moderate/low-grade differentiation. In 150 patients whose survival data was available, Kaplan-Meier analysis revealed a significant (P<0.01) influence on the overall survival for patients with HLA class I-positive tumors compared to those with down-regulation group. The down-regulation of HLA class I expression was an independent poor prognostic factor in patients with pathological stage I NSCLCs. The density of cancer nests-infiltrating CD8+ cells in HLA class I-negative tumors was decreased significantly compared to that in positive or weakly positive tumors (P <0.01). HLA class I expressions did not show a significant correlation with the density of stroma-infiltrating CD8+ cells, or cancer nests-infiltrating CD56 cells, or stroma-infiltrating CD56+ cells. These results suggest that the down-regulation of HLA class I expression may be a poor prognostic factor and affect the density of CD8+ T cells infiltrating in cancer nests of NSCLCs.