甲状腺自身免疫疾病和癌症
在过去的几十年中,许多在体外和体内进行的研究表明,甲状腺自身免疫性疾病和甲状腺癌(TC)(主要是乳头状TC)可能会并发,即使这种关联的确切机制尚不清楚。 TC发生率的增加与自身免疫性甲状腺疾病(AITD)的注册增加吻合,表明这些病理之间存在关联。 TSH水平升高和甲状腺自身免疫被定义为TC的独立危险因素。但是,大量证据表明,自身免疫和炎症本身是TC的危险因素。炎症与TC之间的联系涉及免疫系统,细胞外基质,基质和脂肪组织的多个组成部分,炎症的促肿瘤活性与抗炎作用相反,有利于预防癌症的发展。在肿瘤微环境中,属于先天性(巨噬细胞)和适应性(淋巴细胞)免疫反应的炎性细胞通过细胞因子,趋化因子和脂肪细胞因子与成纤维细胞,内皮细胞,脂肪细胞和细胞外基质相互连接。在转录调节因子(如核因子-κB,促分裂原活化的蛋白激酶或磷酸肌醇-3激酶/蛋白激酶-B)的影响下,与TC的不同亚型相关的癌基因促进了它们对肿瘤微环境的最远增生作用。 。未来的研究对于了解甲状腺自身免疫性与癌症之间的联系将是必要的,同时也需要为AITD的TC患者设计量身定制的疗法。**
Thyroid autoimmune disorders and cancer
In the last decades, many studies conducted in vitro, and in vivo, have shown that thyroid autoimmunity and thyroid cancer (TC) (mainly papillary TC) can be concomitant, even if the exact mechanisms at the basis of this association are still not clear. Growing incidence of TC coincides with increased registration of autoimmune thyroid disorders (AITD) suggesting an association between those pathologies. Elevated TSH levels and thyroid autoimmunity were defined as independent risk factors for TC. However a lot of evidence suggests that autoimmunity and inflammation, per se, are risk factors for TC. The link between inflammation and TC involves multiple components of the immune system, extracellular matrix, stroma, and adipose tissue, with pro-tumoral activity of inflammation being opposed to anti-inflammatory effects, favoring protection against cancer progression. Within the tumor microenvironment, inflammatory cells, belonging both to innate (macrophages) and adaptive (lymphocytes) immune responses, are interconnected with fibroblasts, endothelial cells, adipocytes, and extracellular matrix through cytokines, chemokines and adipocytokines. Under the influence of transcriptional regulators (such as Nuclear Factor-kappa B, mitogen-activated protein kinases, or Phosphoinositide-3 kinase/protein kinase-B), oncogenes connected to the different subtypes of TC promote their farthermost proliferative effect on the tumor microenvironment. Future studies will be necessary to understand the connections between thyroid autoimmunity and cancer, also in order to design a tailored therapy for TC patients with AITD.
pmid: 31158464 Semin Cancer Biol 影响因子: 9.658 发表日期: 20190531 官网 免费下载
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