HLA class I antigen expression is associated with a favorable prognosis in early stage non-small cell lung cancer
HLA class I antigen expression is associated with a favorable prognosis in early stage non-small cell lung cancer
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DOI：
10.1111/j.1349-7006.2007.00558.x
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发表时间：
2007-09-01
期刊：
影响因子：
5.7
通讯作者：
Nishimura, Masaharu
中科院分区：
文献类型：
--
作者：
Kikuchi, Eiki;Yamazaki, Koichi;Nishimura, Masaharu
人类白细胞抗原(人类白细胞抗原)I类显示CD8(+)T淋巴细胞的内源性处理多肽。本研究评估了人类非小细胞肺癌(NSCLC)中人类白细胞抗原I类的表达、临床病理因素和肿瘤浸润性免疫细胞之间的相关性。应用新型抗PAN HLAI类重链抗体EMR8-5免疫组织化学方法检测161例原发非小细胞肺癌组织中HLAI类分子的表达。HLAI类分子的表达分为三类：强阳性、弱阳性和阴性。同时对癌巢和癌间质中的CD8(+)淋巴细胞和CD56(+)自然杀伤细胞进行计数。HLAI类分子表达强阳性50例，弱阳性57例，阴性54例。HLAI类基因表达下调与男性性别、吸烟史、非腺癌组织学类型、中/低分化程度显著相关。HLAI类阴性肿瘤癌巢浸润性CD8(+)细胞密度明显低于HLAI类强阳性肿瘤(P<0.01)。Kaplan-Meier分析显示，HLAI类强阳性表达的患者对总体生存有显著的有利影响(P<；0.01)。多因素分析显示，在病理I期患者中，HLAI类基因表达下调是预后不良的独立因素，而在晚期患者中则不是。提示非小细胞肺癌组织中HLAI类分子表达下调是预后不良的标志之一，这可能在非小细胞肺癌患者的免疫监测中发挥重要作用。
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.