Surgery. Moreover, UTCs express lower levels of acetylated H3 on lysine 18 compared with well-differentiated TCs, suggesting that the deacetylation is a step required for the acquisition of a more aggressive phenotype. Zhang W, Sun W, Qin Y, Wu C, He L, Zhang T, et al. NK cells possess a cytotoxic activity, and their activation depend on two factors: they recognize the stimulatory receptors in the target cells and simultaneously their inhibitor receptors fail to link MHC I molecules on foreign cells. Anticancer Res. The identification of this autocrine protumorigenic loop could represent a therapeutic approach. In PTCs, DCs are immature cells (CD1a+ and S100+) able to secrete cytokines as IL-10 and TGF-β, thereby promoting immune suppressive response (90). doi: 10.3892/ijo.2013.1913. CSCs are a small subset of cancer cells within tumors that exhibit exclusive self-renewal ability, clonogenic, and metastatic potential. Recently, many in vitro and in vivo studies have reported that treatment with HDAC inhibitors alone or in combination with chemotherapy or other biological agent induces apoptosis and cell cycle arrest, impairing the growth while incrementing the radioiodine uptake of TC cells (64). Wulf GG, Luo KL, Jackson KA, Brenner MK, Goodell MA. Cancer cells establish a complex relationship with the surrounding stromal cells such as cancer-associated fibroblasts (CAFs). Eur J Biochem (1995) 230(2):576–81. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cancer-associated fibroblasts (CAFs) produce FGF-21, which favors a more aggressive TC cells phenotype. Biochim Biophys Acta (2008) 1782(2):61–74. Unfortunately, some clinical limitations have been associated with the use of the epigenetic inhibitors in many solid tumors, including TC, as remethylation, the lack of specificity and general toxicity. Figure 4. doi: 10.1016/j.bbrc.2015.12.008, 58. KISS1 and KISS1R expression in primary and metastatic colorectal cancer. Minerva Endocrinol. Immunotherapy is based on the use of anti-PD1 antibodies as Pembrolizumab and Nivolumab, whereas epigenetic therapy nowadays is limited to histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors alone or in combination with conventional approaches in TCs. J Exp Clin Cancer Res. Here, we highlight the key points related to the most relevant epigenetic mechanisms altered in the different subtypes of TCs: (i) Thyroid-specific differentiation and tumor suppressor genes aberrantly methylated in their promoter regions along with altered expression of miRNAs represent the most frequent epigenetic features in well-differentiated thyroid tumors, as PTC and FTC, while the amount of reports regarding the histone modifications are very limited.