Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Federal University of São Paulo, São Paulo, Brazil.
Division of Emergency Medicine and Evidence-Based Medicine, Federal University of São Paulo, São Paulo, Brazil.
Rev Endocr Metab Disord. 2024 Feb;25(1):5-17. doi: 10.1007/s11154-023-09846-w. Epub 2023 Oct 27.
The recent incorporation of immune checkpoint inhibitors targeting the PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways into the therapeutic armamentarium of cancer has increased the need to understand the correlation between the immune system, autoimmunity, and malignant neoplasms. Both autoimmune thyroid diseases and thyroid cancer are common clinical conditions. The molecular pathology of autoimmune thyroid diseases is characterized by the important impact of the PD-1/PD-L1 axis, an important inhibitory pathway involved in the regulation of T-cell responses. Insufficient inhibitory pathways may prone the thyroid tissue to a self-destructive immune response that leads to hypothyroidism. On the other hand, the PD-1/PD-L1 axis and other co-inhibitory pathways are the cornerstones of the immune escape mechanisms in thyroid cancer, which is a mechanism through which the immune response fails to recognize and eradicate thyroid tumor cells. This common mechanism raises the idea that thyroid autoimmunity and thyroid cancer may be opposite sides of the same coin, meaning that both conditions share similar molecular signatures. When associated with thyroid autoimmunity, thyroid cancer may have a less aggressive presentation, even though the molecular explanation of this clinical consequence is unclear. More studies are warranted to elucidate the molecular link between thyroid autoimmune disease and thyroid cancer. The prognostic impact that thyroid autoimmune disease, especially chronic lymphocytic thyroiditis, may exert on thyroid cancer raises important insights that can help physicians to better individualize the management of patients with thyroid cancer.
近年来，针对 PD-1（程序性细胞死亡受体 1）和 CTLA-4（细胞毒性 T 淋巴细胞相关抗原 4）通路的免疫检查点抑制剂被纳入癌症治疗武器库，这增加了人们对免疫系统、自身免疫和恶性肿瘤之间相关性的理解的需求。自身免疫性甲状腺疾病和甲状腺癌都是常见的临床情况。自身免疫性甲状腺疾病的分子病理学的特点是 PD-1/PD-L1 轴的重要影响，这是一个参与调节 T 细胞反应的重要抑制途径。抑制途径不足可能使甲状腺组织容易发生导致甲状腺功能减退的自身破坏性免疫反应。另一方面，PD-1/PD-L1 轴和其他共抑制途径是甲状腺癌免疫逃逸机制的基石，这是一种免疫反应未能识别和消除甲状腺肿瘤细胞的机制。这种共同的机制提出了这样一种想法，即甲状腺自身免疫和甲状腺癌可能是同一枚硬币的两面，这意味着这两种情况具有相似的分子特征。当与甲状腺自身免疫相关时，甲状腺癌的表现可能不那么具有侵袭性，尽管这种临床后果的分子解释尚不清楚。需要更多的研究来阐明甲状腺自身免疫性疾病与甲状腺癌之间的分子联系。甲状腺自身免疫性疾病，特别是慢性淋巴细胞性甲状腺炎，可能对甲状腺癌产生的预后影响提供了重要的见解，可以帮助医生更好地对甲状腺癌患者进行个体化管理。
