Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Hum Immunol. 2012 Oct;73(10):1017-22. doi: 10.1016/j.humimm.2012.07.325. Epub 2012 Jul 23.
Natural killer (NK) cells are key members of innate immunity against tumor and infection. Killer cell immunoglobulin-like receptor (KIR) genes regulates NK cell function, which varies substantially between individuals in the number and type. Specific KIRs are associated with certain diseases. Herein we investigated if KIR genes are associated with thyroid cancer risk. Eighty-five patients with thyroid cancer were characterized for the presence and absence of 11 variable KIR genes using a gene-specific PCR typing system, and compared with our recently published healthy control data. Overall, a trend toward more activating KIR receptors was observed in thyroid cancer patients compared to the healthy controls. Particularly, the activating KIR2DS5 gene was significantly increased in patients compared to the controls. Additionally, three other genes (3DS1-2DL5-2DS1) that are strongly linked to KIR2DS5 at the telomeric region of the KIR gene complex [called Telomeric 4 (T4) gene cluster] were also more predominant in the thyroid cancer patient group than in healthy controls. A similar trend of having more of the T4 gene cluster was also reported in a previous study with cervical neoplasia. Together, these data suggest that specific activating KIR genes in cancer patients could generate a chronic inflammatory condition resulting in a tumor microenvironment that may favor tumor growth.
自然杀伤 (NK) 细胞是固有免疫抵抗肿瘤和感染的关键成员。杀伤细胞免疫球蛋白样受体 (KIR) 基因调节 NK 细胞的功能,个体之间的 KIR 数量和类型存在很大差异。特定的 KIR 与某些疾病相关。在此,我们研究了 KIR 基因是否与甲状腺癌风险相关。使用基因特异性 PCR 分型系统,对 85 例甲状腺癌患者进行了 11 种可变 KIR 基因的存在和缺失特征分析,并与我们最近发表的健康对照组数据进行了比较。总体而言,与健康对照组相比,甲状腺癌患者中具有更多激活型 KIR 受体的趋势。特别是,与对照组相比,激活型 KIR2DS5 基因在患者中显著增加。此外,在 KIR 基因复合体的端粒区域(称为端粒 4 [T4] 基因簇)与 KIR2DS5 紧密相关的另外三个基因(3DS1-2DL5-2DS1)在甲状腺癌患者组中也更为常见。在之前的宫颈癌研究中也报道了类似的趋势,即 T4 基因簇的数量更多。这些数据表明,癌症患者中特定的激活型 KIR 基因可能会产生慢性炎症状态,导致肿瘤微环境有利于肿瘤生长。