Tamaki Shigehiro, Kawakami Masayoshi, Yamanaka Yasutsugu, Shimomura Hiroyuki, Imai Yuichiro, Ishida Jun-ichi, Yamamoto Kazuhiko, Ishitani Akiko, Hatake Katsuhiko, Kirita Tadaaki
Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Clin Immunol. 2009 Mar;130(3):331-7. doi: 10.1016/j.clim.2008.09.004. Epub 2008 Oct 23.
NK and cytotoxic T cells play an important role in the elimination of virus-infected and tumor cells through NKG2D activating receptors, which can promote the lysis of target cells by binding to the major histocompatibility complex class I-related chain A (MICA) proteins. Polymorphisms in MICA may influence its binding to the NKG2D. The soluble form of MICA is released from the surface of tumor cells of epithelial origin. Whereas MICA expressed on the cell surface stimulates the immunoreceptor natural killer group 2, member D (NKG2D), the secreted form down-regulates NKG2D activity, thus allowing the tumor to escape immunosurveillance by NKG2D-expressing cells. In this study, we examined the association between MICA gene microsatellite polymorphisms and serum levels of soluble MICA in patients with oral squamous cell carcinoma (OSCC). We found that patients with OSCC were more likely to have the A5.1 allele when compared to healthy subjects and also more likely to be homozygous for this allele (p=0.041). Patients with the homozygous A5.1 genotype had higher levels of soluble MICA (p=0.031) and a lower survival rate (p=0.026).
自然杀伤细胞（NK）和细胞毒性T细胞通过NKG2D激活受体在清除病毒感染细胞和肿瘤细胞过程中发挥重要作用，该受体可通过与主要组织相容性复合体I类相关链A（MICA）蛋白结合来促进靶细胞的裂解。MICA的多态性可能影响其与NKG2D的结合。可溶性MICA是从上皮来源的肿瘤细胞表面释放的。细胞表面表达的MICA刺激免疫受体自然杀伤细胞2族成员D（NKG2D），而分泌形式则下调NKG2D活性，从而使肿瘤能够逃避表达NKG2D细胞的免疫监视。在本研究中，我们检测了口腔鳞状细胞癌（OSCC）患者中MICA基因微卫星多态性与可溶性MICA血清水平之间的关联。我们发现，与健康受试者相比，OSCC患者更有可能携带A5.1等位基因，并且该等位基因纯合的可能性也更高（p = 0.041）。A5.1基因型纯合的患者可溶性MICA水平更高（p = 0.031），生存率更低（p = 0.026）。
