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Clinical and molecular impact of concurrent thyroid autoimmune disease and thyroid cancer: From the bench to bedside

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Abstract

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.

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Acknowledgement

The authors thank FAPESP and CNPq for grants and funding for research.

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This work did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.  Fundação de Amparo à Pesquisa do Estado de São Paulo, 2021/02752-6, 2021/02752-6, 2021/02752-6, 2021/02752-6, Thyroid Department, Sociedade Brasileira de Endocrinologia e Metabologia.

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  1. Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Federal University of São Paulo, São Paulo, Brazil

    Victor Alexandre dos Santos Valsecchi, Felipe Rodrigues Betoni & Lucas Leite Cunha

  2. Division of Emergency Medicine and Evidence-Based Medicine, Federal University of São Paulo, São Paulo, Brazil

    Victor Alexandre dos Santos Valsecchi, Felipe Rodrigues Betoni & Lucas Leite Cunha

  3. Laboratory of Cancer Molecular Genetics, School of Medical Sciences, State University of Campinas (Unicamp), Campinas, Brazil

    Laura Sterian Ward

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VASV, FRB, LSW, and LLC wrote the main manuscript text, participated in conception and design, critical review of the literature and data, composition of the manuscript, and final approval. VASV prepared the figures. VASV and FRB prepared the table. LSW and LLC promoted clinical and translational orientation. VASV, FRB, and LLC prepared the selection of notable articles for review, and critical review of the literature and data. All authors reviewed the manuscript.

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dos Santos Valsecchi, V.A., Betoni, F.R., Ward, L.S. et al. Clinical and molecular impact of concurrent thyroid autoimmune disease and thyroid cancer: From the bench to bedside. Rev Endocr Metab Disord 25, 5–17 (2024). https://doi.org/10.1007/s11154-023-09846-w

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