Clinical relevance and functional implications for human leucocyte antigen-g expression in non-small-cell lung cancer

摘要

HLA-G has been documented both in establishment of anti-tumour immune responses and in tumour evasion. To investigate the clinical relevance of HLA-G in non-small-cell lung cancer (NSCLC), expression status and potential significance of HLA-G in NSCLC were analysed. In this study, HLA-G expression in 101 NSCLC primary lesions and plasma soluble HLA-G (sHLA-G) from 91 patients were analysed with immunohistochemistry and ELISA, respectively. Correlations between HLA-G status and various clinical parameters including survival time were evaluated. Meanwhile, functional analysis of transfected cell surface HLA-G expression and plasma sHLA-G form NSCLC patients on natural killer (NK) cell cytolysis were performed. Data revealed that HLA-G was expressed in 41.6% (42/101) NSCLC primary lesions, while undetectable in adjacent normal lung tissues. HLA-G expression in NSCLC lesions was strongly correlated to disease stages (P= 0.002). Plasma sHLA-G from NSCLC patients was markedly higher than that in normal controls (P= 0.004), which was significantly associated with the disease stages (I versus IV, P= 0.025; II versus IV, P= 0.029). Patient plasma sHLA-G level (≥median, 32.0 U/ml) had a significantly shorter survival time (P= 0.044); however, no similar significance was observed for the lesion HLA-G expression. In vitro data showed that both cell surface HLA-G and patient plasma sHLA-G could dramatically decrease the NK cell cytolysis. Our findings indicated that both lesion HLA-G expression and plasma sHLA-G in NSCLC is related to the disease stage and can exert immunosuppression to the NK cell cytolysis, indicating that HLA-G could be a potential therapeutic target. Moreover, plasma sHLA-G in NSCLC patients could be used as a prognosis factor for NSCLC.