Immune responses in the thyroid cancer microenvironment: making immunotherapy a possible mission

Abstract

The incidence of thyroid cancers has been steadily increasing worldwide over the past few decades. Although five-year survival rates for differentiated thyroid cancers are upwards of 90%, clinical outcomes for patients with undifferentiated, recurrent and/or metastatic disease are often dismal despite conventional interventions. As such, there is a demand for novel treatment options. Cancer immunotherapy represents the ultimate form of personalized medicine by leveraging the specificity and potency of a patient's immune system to kill their tumor. The thyroid cancer microenvironment is rich in immunological cells, making it a reasonable candidate for immunotherapy. This review maps out the immunological features of thyroid cancers and how these can be modulated. There are surprising immunological consequences of conventional therapies that demand attention. Also, hormonal modulation of the immune system is highlighted as a unique and confounding feature of thyroid cancers. A variety of cuttingedge immune-based therapies are discussed, with an emphasis placed on how these can be integrated with the current standard of care. Several high priority areas in need of research are also highlighted.

Nevirapine inhibits migration and invasion in dedifferentiated thyroid cancer cells

“…Nevirapine, as an immunomodulator, has been shown to inhibit the secretion of cytokine IL‐6 in HIV‐infected patients . Accumulating studies suggest that thyroid cancer is also an autoimmune disease . We found that nevirapine could inhibit IL‐6 mRNA expression in thyroid cancer by RT‐PCR.…”

“…29 Accumulating studies suggest that thyroid cancer is also an autoimmune disease. [30][31][32] We found that nevirapine could inhibit IL-6 mRNA expression in thyroid cancer by RT-PCR. To elucidate the mechanism underlying the effects of IL-6 in thyroid cancer, we assessed the expression of its downstream genes.…”

Molecular Heterogeneity of Papillary Thyroid Cancer: Comparison of Primary Tumors and Synchronous Metastases in Regional Lymph Nodes by Mass Spectrometry Imaging

“…These not only include remodeling of tumor niche (e.g., reorganization of extracellular matrix and formation of blood vessels) but also production of cytokines and growth factors that increase motility and invasiveness of cancer cells as well as decrease their sensitivity to pro-death factors [40,41]. Immune cells have an obvious role also in the development and progression of thyroid cancers [42,43]. On the other hand, phenotypic differences between a primary tumor and its lymph node metastases could also reflect invasionrelated features of metastatic cells.…”

Expression levels of ARHI and Beclin1 in thyroid cancer and their relationship with clinical pathology and prognosis

“…further research and treatment of thyroid cancer in microenvironment are required. The value of ARHI and Beclin1 in the study of the expression level of thyroid cancer is very high, mainly because the tumor cells can be killed through the function of the immune system; the microenvironment in the body of cancer patients is rich in immune cells, and immunotherapy is the ultimate treatment (25). The effects of ARHI and Beclin1 genes on the formation of thyroid tumor cells and the related mechanisms were also analyzed at the histological level of human thyroid cancer, which provided theoretical basis for the targeted treatment of thyroid cancer.…”