The Immune Landscape of Thyroid Cancer in the Context of Immune Checkpoint Inhibition
AbstractImmune cells play critical roles in tumor prevention as well as initiation and progression. However, immune-resistant cancer cells can evade the immune system and proceed to form tumors. The normal microenvironment (immune cells, fibroblasts, blood and lymphatic vessels, and interstitial extracellular matrix (ECM)) maintains tissue homeostasis and prevents tumor initiation. Inflammatory mediators, reactive oxygen species, cytokines, and chemokines from an altered microenvironment promote tumor growth. During the last decade, thyroid cancer, the most frequent cancer of the endocrine system, has emerged as the fifth most incident cancer in the United States (USA), and its incidence is steadily growing. Inflammation has long been associated with thyroid cancer, raising critical questions about the role of immune cells in its pathogenesis. A plethora of immune cells and their mediators are present in the thyroid cancer ecosystem. Monoclonal antibodies (mAbs) targeting immune checkpoints, such as mAbs anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA-4) and anti-programmed cell death protein-1/programmed cell death ligand-1 (anti-PD-1/PD-L1), have revolutionized the treatment of many malignancies, but they induce thyroid dysfunction in up to 10% of patients, presumably by enhancing autoimmunity. Combination strategies involving immune checkpoint inhibitors (ICIs) with tyrosine kinase (TK) or serine/threonine protein kinase B-raf (BRAF) inhibitors are showing considerable promise in the treatment of advanced thyroid cancer. This review illustrates how different immune cells contribute to thyroid cancer development and the rationale for the antitumor effects of ICIs in combination with BRAF/TK inhibitors. View Full-Text
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Varricchi, G.; Loffredo, S.; Marone, G.; Modestino, L.; Fallahi, P.; Ferrari, S.M.; de Paulis, A.; Antonelli, A.; Galdiero, M.R. The Immune Landscape of Thyroid Cancer in the Context of Immune Checkpoint Inhibition. Int. J. Mol. Sci. 2019, 20, 3934.
Varricchi G, Loffredo S, Marone G, Modestino L, Fallahi P, Ferrari SM, de Paulis A, Antonelli A, Galdiero MR. The Immune Landscape of Thyroid Cancer in the Context of Immune Checkpoint Inhibition. International Journal of Molecular Sciences. 2019; 20(16):3934.Chicago/Turabian Style
Varricchi, Gilda; Loffredo, Stefania; Marone, Giancarlo; Modestino, Luca; Fallahi, Poupak; Ferrari, Silvia M.; de Paulis, Amato; Antonelli, Alessandro; Galdiero, Maria R. 2019. "The Immune Landscape of Thyroid Cancer in the Context of Immune Checkpoint Inhibition." Int. J. Mol. Sci. 20, no. 16: 3934.
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