Abstract
A hallmark of cancer is the ability of tumor cells to avoid immune destruction. Activated immune cells in tumor microenvironment (TME) secrete proinflammatory cytokines and chemokines which foster the proliferation of tumor cells. Specific antigens expressed by cancer cells are recognized by the main actors of immune response that are involved in their elimination (immunosurveillance). By the recruitment of immunosuppressive cells, decreasing the tumor immunogenicity, or through other immunosuppressive mechanisms, tumors can impair the host immune cells within the TME and escape their surveillance. Within the TME, cells of the innate (e.g., macrophages, mast cells, neutrophils) and the adaptive (e.g., lymphocytes) immune responses are interconnected with epithelial cancer cells, fibroblasts, and endothelial cells via cytokines, chemokines, and adipocytokines. The molecular pattern of cytokines and chemokines has a key role and could explain the involvement of the immune system in tumor initiation and progression. Thyroid cancer-related inflammation is an important target for diagnostic procedures and novel therapeutic strategies. Anticancer immunotherapy, especially immune checkpoint inhibitors, unleashes the immune system and activates cytotoxic lymphocytes to kill cancer cells. A better knowledge of the molecular and immunological characteristics of TME will allow novel and more effective immunotherapeutic strategies in advanced thyroid cancer.
Highlights
The characteristics that a normal cell must obtain, to develop malignancy, are the intrinsic ones of the tumor cell and the susceptibility to an inflammatory tumor microenvironment (TME) [1,2]
When natural killer (NK) cells are cocultured with anaplastic thyroid cancers (ATCs), which expresses elevated levels of COX2, the NKG2D was downregulated, when compared to those cocultured with COX2-negative cell lines [72]
In primary cultures of thyroid follicular cells (TFC) and papillary thyroid cancers (PTCs), we reported that IP-10 was not released basally, but IFN-γ stimulated its secretion in a similar manner in both cell types, while TNF-α alone induced a slight but significant IP-10 secretion only in PTCs [146]
Summary
The characteristics that a normal cell must obtain, to develop malignancy, are the intrinsic ones of the tumor cell (e.g., cell-autonomous growth and resistance to apoptosis) and the susceptibility to an inflammatory tumor microenvironment (TME) [1,2]. Regulatory T cells (Tregs) (CD4+/CD25+ T lymphocytes) are elevated in primary and metastatic tumors and they are associated with poor prognosis [12] These cells exert their immunosuppressive action producing cytokines (i.e., interleukin (IL)-10, transforming growth factor (TGF)-β, and IL-35) or inhibiting the activation of the T-cell receptor (TCR) [13]. For these reasons, Tregs are a potential therapeutic target which can improve tumor immunity and eventually provide clinical benefit [14]. In a model of pancreatic ductal adenocarcinoma, Tregs suppressed the function of tumor-infiltrating DCs, inhibiting the expression of co-stimulatory ligands and the activation of CD8+ T cells [42]. The function of tumor-infiltrating DCs can be restored by blocking immunosuppressive pathways, such as those associated with PD-1, secretion of IL-10, and production of lactic acid [40,44]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
