Upregulated expression of NKG2D and its ligands give potential therapeutic targets for patients with thymoma
Upregulated expression of NKG2D and its ligands give potential therapeutic targets for patients with thymoma
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NKG2D及其配体表达上调为胸腺瘤患者提供潜在的治疗靶点
DOI：
10.1038/cgt.2015.29
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发表时间：
2015-07-01
影响因子：
6.4
通讯作者：
Du, Y.
中科院分区：
文献类型：
--
作者：
Xuan, X. Y.;Zhang, J. F.;Du, Y.
NK细胞的激活受体NKG2D （natural killer group 2，成员D）通过靶向选择性诱导于癌细胞的配体，促进肿瘤免疫监视，在抗肿瘤免疫应答中具有重要作用。由于这些配体在健康成人组织中不广泛表达，因此NKG2D配体可能成为癌症免疫治疗方法的有用靶点。在本研究中，为了阐明NKG2D - NKG2D配体相互作用在胸腺瘤组织中的作用，并评估NKG2D配体作为胸腺瘤治疗靶点的潜在作用，我们检测了NKG2D及其特异性配体的表达：免疫组化和反转录-实时荧光定量pcr检测36例胸腺瘤（6例A亚型、6例AB亚型、8例B1亚型、5例B2亚型、6例B3亚型和5例C亚型）、15例胸腺萎缩和8例胸腺增生的MICA（主要组织相容性复合体I类链相关蛋白A）、MICB（主要组织相容性复合体I类链相关蛋白B）和ULBP （ul16结合蛋白）。我们发现，与萎缩胸腺和增生胸腺相比，六种胸腺瘤中NKG2D、MICA、MICB和ULBP的mRNA和蛋白水平均上调。此外，发现NKG2D配体经常在胸腺瘤细胞上共表达。MICA、MICB和ULBP在C亚型中的表达高于A、AB、B1、B2和B3亚型。因此，我们认为胸腺瘤患者中存在NKG2D、MICA、MICB和ULBP1的高表达，这可能增强了NK细胞对肿瘤细胞的识别功能。MICA， MICB和ULBP是胸腺瘤治疗的一个有吸引力的靶点。NKG2D、MICA、MICB、ULBP1的异常表达可以为我们提供胸腺瘤发生的证据，也可以作为胸腺瘤治疗的靶点。
The activating receptor NKG2D (natural killer group 2, member D) of natural killer (NK) cells promotes tumor immune surveillance by targeting ligands selectively induced on cancer cells, and thus having an important role in antitumor immune response. Because these ligands are not widely expressed on healthy adult tissue, NKG2D ligands may present as useful target for immunotherapeutic approaches in cancer. In this study, to elucidate the role of NKG2D–NKG2D ligand interaction in thymoma tissues and to evaluate the potential role of NKG2D ligands as therapeutic target for thymoma, we examined the expression of NKG2D and its specific ligands: MICA (major histocompatibility complex class I chain-related protein A), MICB (major histocompatibility complex class I chain-related protein B) and ULBP (UL16-binding protein) in 36 thymomas (6 subtype A, 6 subtype AB, 8 subtype B1, 5 subtype B2, 6 subtype B3 and 5 subtype C), 15 thymic atrophy and 8 thymic hyperplasia by immunohistochemistry and reverse transcription-real-time-PCR methods. We demonstrated that both mRNA and protein levels of NKG2D, MICA, MICB and ULBP were upregulated in six types of thymomas compared with those in atrophic thymus or proliferating thymus. Furthermore, the NKG2D ligands were found to be frequently coexpressed on thymoma cells. Furthermore, the expression of MICA, MICB and ULBP in subtype C was higher compared with those in subtype A, AB, B1, B2 and B3. Thus, we concluded that high expressions of NKG2D, MICA, MICB and ULBP1 were shown in patients with thymoma, and this may enhance the recognition function of NK cells to eliminate tumor cells. MICA, MICB and ULBP presented an attractive target for thymoma therapy. The abnormal expression of NKG2D, MICA, MICB and ULBP1 can provide us with evidence of the occurrence of thymoma and could also be used as a target in the treatment of thymoma.