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HLA class I antigen expression is associated with a favorable prognosis in early stage non‐small cell lung cancer

2007; Wiley; Volume: 98; Issue: 9 Linguagem: Inglês

10.1111/j.1349-7006.2007.00558.x

1349-7006

Eiki Kikuchi, Koichi Yamazaki, Toshihiko Torigoe, Yasushi Cho, Masaki Miyamoto, Satoshi Oizumi, Fumihiro Hommura, Hirotoshi Dosaka‐Akita, Masaharu Nishimura,

Immune Cell Function and Interaction

Human leukocyte antigen (HLA) class I displays a repertoire of endogenously processed peptides to CD8 + T lymphocytes. The present study assessed correlations between HLA class I expression, clinicopathologic factors, and tumor‐infiltrating immune cells in human non‐small cell lung cancers (NSCLC). Expression of HLA class I was assessed in 161 resected primary NSCLC by immunohistochemistry using EMR8–5, a novel monoclonal anti‐pan HLA class I heavy chain antibody. Expression of HLA class I was classified into three categories: strongly positive, weakly positive, or negative. Tumor‐infiltrating CD8 + lymphocytes and CD56 + natural killer cells within cancer nests and stroma were also counted. Expression of HLA class I was strongly positive in 50 tumors, weakly positive in 57 tumors, and negative in 54 tumors. Down‐regulation of HLA class I was significantly correlated with male sex, history of smoking, non‐adenocarcinoma histology, and moderate‐/low‐grade differentiation. The density of cancer nest‐infiltrating CD8 + cells in HLA class I‐negative tumors was significantly decreased compared to that in HLA class I strongly positive tumors ( P < 0.01). Kaplan–Meier analysis revealed a significant favorable influence on overall survival for patients displaying tumors with strongly positive expression of HLA class I ( P < 0.01). Multivariate analysis revealed down‐regulation of HLA class I as an independent factor of poor prognosis in pathological stage I patients, but not in late‐stage patients. These results suggest that down‐regulation of HLA class I expression in NSCLC is a marker of poor prognosis, and this may play a critical role in immune surveillance of patients with NSCLC. ( Cancer Sci 2007; 98: 1424–1430)