Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Front Endocrinol (Lausanne). 2021 Apr 27;11:637826. doi: 10.3389/fendo.2020.637826. eCollection 2020.
Immune system plays a key role in cancer prevention as well as in its initiation and progression. During multistep development of tumors, cells must acquire the capability to evade immune destruction. Both and studies showed that thyroid tumor cells can avoid immune response by promoting an immunosuppressive microenvironment. The recruitment of immunosuppressive cells such as TAMs (tumor-associated macrophages), TAMCs (tumor-associated mast cells), MDSC (myeloid-derived suppressor cells), TANs (tumor-associated neutrophils) and Tregs (regulatory T cells) and/or the expression of negative immune checkpoints, like PD-L1 (programmed death-ligand 1), CTLA-4 (cytotoxic T-lymphocyte associated protein 4), and/or immunosuppressive enzymes, as IDO1 (indoleamine 2,3-dioxygenase 1), are just some of the mechanisms that thyroid cancer cells exploit to escape immune destruction. Some authors systematically characterized immune cell populations and soluble mediators (chemokines, cytokines, and angiogenic factors) that constitute thyroid cancer microenvironment. Their purpose was to verify immune system involvement in cancer growth and progression, highlighting the differences in immune infiltrate among tumor histotypes. More recently, some authors have provided a more comprehensive view of the relationships between tumor and immune system involved in thyroid carcinogenesis. The Cancer Genome Atlas (TCGA) delivered a large amount of data that allowed to combine information on the inflammatory microenvironment with gene expression data, genetic and clinical-pathological characteristics, and differentiation degree of papillary thyroid carcinoma (PTC). Moreover, using a new sensitive and highly multiplex analysis, the NanoString Technology, it was possible to divide thyroid tumors in two main clusters based on expression of immune-related genes. Starting from these results, the authors performed an immune phenotype analysis that allowed to classify thyroid cancers in hot, cold, or intermediate depending on immune infiltration patterns of the tumor microenvironment. The aim of this review is to provide a comprehensive and updated view of the knowledge on immune landscape of thyroid tumors. Understanding interactions between tumor and microenvironment is crucial to effectively direct immunotherapeutic approaches in the treatment of thyroid cancer, particularly for those not responsive to conventional therapies.
免疫系统在癌症的预防、起始和进展中起着关键作用。在肿瘤的多步骤发展过程中,细胞必须获得逃避免疫破坏的能力。 和 研究均表明,甲状腺肿瘤细胞可以通过促进免疫抑制微环境来避免免疫反应。免疫抑制细胞(如 TAMs(肿瘤相关巨噬细胞)、TAMCs(肿瘤相关肥大细胞)、MDSC(髓源抑制细胞)、TANs(肿瘤相关中性粒细胞)和 Tregs(调节性 T 细胞)的募集)和/或负免疫检查点(如 PD-L1(程序性死亡配体 1)、CTLA-4(细胞毒性 T 淋巴细胞相关蛋白 4)和/或免疫抑制酶,如 IDO1(吲哚胺 2,3-双加氧酶 1)的表达)只是甲状腺癌细胞逃避免疫破坏所利用的一些机制。一些作者系统地描述了构成甲状腺癌微环境的免疫细胞群体和可溶性介质(趋化因子、细胞因子和血管生成因子)。他们的目的是验证免疫系统在癌症生长和进展中的参与,并强调肿瘤组织类型之间免疫浸润的差异。最近,一些作者更全面地描述了甲状腺癌发生过程中肿瘤与免疫系统之间的关系。癌症基因组图谱(TCGA)提供了大量的数据,使人们能够将炎症微环境的信息与基因表达数据、遗传和临床病理特征以及甲状腺乳头状癌(PTC)的分化程度相结合。此外,使用新的敏感和高度多重分析纳米字符串技术,有可能根据免疫相关基因的表达将甲状腺肿瘤分为两个主要簇。基于这些结果,作者进行了免疫表型分析,根据肿瘤微环境的免疫浸润模式将甲状腺癌分为热、冷或中间型。本文综述的目的是提供对甲状腺肿瘤免疫景观的全面和最新的认识。了解肿瘤与微环境之间的相互作用对于有效指导甲状腺癌的免疫治疗方法至关重要,特别是对于那些对传统疗法无反应的患者。