Department of Otorhinolaryngology, Antoine Lacassagne Center, Nice, France.
Curr Med Chem. 2010;17(30):3449-61. doi: 10.2174/092986710792927804.
Chronic infection and inflammation contribute to around 25% of cancer cases worldwide. While a direct link between several types of human malignancies and inflammation has now been established, in particular at the gastrointestinal level, the relationship between inflammation and thyroid cancer and the pathophysiology of chronic inflammation that induces papillary thyroid carcinoma (PTC) are still subjects of debate. However, several epidemiological and morphological studies have strongly suggested an increased risk of PTC in patients with Hashimoto's thyroiditis (HT). As in HT, an intense immune infiltrate is associated with certain PTC and might play a critical role in the regulation of carcinogenesis and in carcinoma progression. Proinflammatory molecules, such as cytokines and chemokines, which are produced by immune infiltrate in the tumor microenvironment, contribute to the regulation of key cellular processes for cancer onset and progression, in particular for tumor cell proliferation, apoptosis, autophagy, angiogenesis and metastasis. Molecular studies have identified activation of the RET/PTC rearrangement-induced MAPK signaling pathway as the driving force in the development of PTC in the context of HT. These genetic alterations may be favored by chronic inflammation. In this regard, the RET oncoprotein and its downstream effectors, such as those implicated in the activation of the MAPK pathway, as well as inflammatory molecules of the tumor microenvironment could be promising molecular targets for new therapeutic strategies for thyroid cancer. This review focuses on the complex link between thyroid cancer and chronic inflammation and highlights the different current hypotheses regarding the role of the immune cell microenvironment in the initiation and progression of PTC.
慢性感染和炎症导致全球约 25%的癌症病例。虽然几种人类恶性肿瘤与炎症之间的直接联系现已确定，特别是在胃肠道水平，但炎症与甲状腺癌之间的关系以及导致甲状腺乳头状癌（PTC）的慢性炎症的病理生理学仍然存在争议。然而，几项流行病学和形态学研究强烈表明桥本甲状腺炎（HT）患者的 PTC 风险增加。与 HT 一样，强烈的免疫浸润与某些 PTC 相关，可能在调节癌发生和癌进展中发挥关键作用。炎症分子，如细胞因子和趋化因子，由肿瘤微环境中的免疫浸润产生，有助于调节癌症发生和进展的关键细胞过程，特别是肿瘤细胞增殖、凋亡、自噬、血管生成和转移。分子研究已经确定，在 HT 背景下，RET/PTC 重排诱导的 MAPK 信号通路的激活是 PTC 发展的驱动力。这些遗传改变可能受到慢性炎症的影响。在这方面，RET 癌蛋白及其下游效应物，如参与 MAPK 通路激活的那些，以及肿瘤微环境中的炎症分子，可能是甲状腺癌新治疗策略的有前途的分子靶点。这篇综述重点介绍了甲状腺癌与慢性炎症之间的复杂联系，并强调了关于免疫细胞微环境在 PTC 起始和进展中的作用的不同当前假设。
