Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
PLoS One. 2013;8(4):e61024. doi: 10.1371/journal.pone.0061024. Epub 2013 Apr 2.
NK cells are a major component of the antitumour immune response that limits tumour progression. However, it has been reported that tumour-infiltrating NK (TINK) cells from patients with non-small-cell lung carcinoma (NSCLC) exhibit profound defects in degranulation and IFN-γ production. In support of this notion, we report a novel mechanism associated with tumour escape from NK cell-mediated antitumour immunity in lung carcinoma. In this study, we investigated the phenotypic profile of TINK cells based on the expression of the NK-cell maturation markers CD11b and CD27. Interestingly, we found a substantial CD11b(-)CD27(-) (DN) NK-cell population harboured within the tumour tissues. The presence of this CD11b(-)CD27(-) NK subset indicated that the TINK cells were of an immature and inactive phenotype. Remarkably, we determined that the presence of DN NK cells had an impact on the clinical outcomes of patients with NSCLC, as the frequency of tumour-infiltrating DN NK cells was positively correlated with the tumour stage and tumour size. We further used a murine Lewis lung cancer (LLC) model to confirm the correlation between the frequency of tumour-infiltrating DN NK cells and the progression of lung carcinoma. Together, our findings demonstrate that the tumour microenvironment may render TINK cells less tumouricidal and thereby contribute to cancer progression.
自然杀伤 (NK) 细胞是抗肿瘤免疫反应的主要组成部分，可限制肿瘤的进展。然而，据报道，非小细胞肺癌 (NSCLC) 患者的肿瘤浸润 NK (TINK) 细胞在脱颗粒和 IFN-γ 产生方面存在严重缺陷。支持这一观点，我们报告了一种与肺癌中 NK 细胞介导的抗肿瘤免疫逃逸相关的新机制。在这项研究中，我们根据 NK 细胞成熟标志物 CD11b 和 CD27 的表达来研究 TINK 细胞的表型特征。有趣的是，我们发现肿瘤组织中存在大量 CD11b(-)CD27(-)（DN）NK 细胞群。该 CD11b(-)CD27(-) NK 亚群的存在表明 TINK 细胞具有不成熟和无活性的表型。值得注意的是，我们确定 DNNK 细胞的存在对 NSCLC 患者的临床结局有影响，因为肿瘤浸润性 DNNK 细胞的频率与肿瘤分期和肿瘤大小呈正相关。我们进一步使用小鼠 Lewis 肺癌 (LLC) 模型来证实肿瘤浸润性 DNNK 细胞的频率与肺癌进展之间的相关性。总之，我们的研究结果表明，肿瘤微环境可能使 TINK 细胞的肿瘤杀伤能力降低，从而促进癌症的进展。
