Abstract
Immune system plays a key role in cancer prevention as well as in its initiation and progression. During multistep development of tumors, cells must acquire the capability to evade immune destruction. Both in vitro and in vivo studies showed that thyroid tumor cells can avoid immune response by promoting an immunosuppressive microenvironment. The recruitment of immunosuppressive cells such as TAMs (tumor-associated macrophages), TAMCs (tumor-associated mast cells), MDSC (myeloid-derived suppressor cells), TANs (tumor-associated neutrophils) and Tregs (regulatory T cells) and/or the expression of negative immune checkpoints, like PD-L1 (programmed death-ligand 1), CTLA-4 (cytotoxic T-lymphocyte associated protein 4), and/or immunosuppressive enzymes, as IDO1 (indoleamine 2,3-dioxygenase 1), are just some of the mechanisms that thyroid cancer cells exploit to escape immune destruction. Some authors systematically characterized immune cell populations and soluble mediators (chemokines, cytokines, and angiogenic factors) that constitute thyroid cancer microenvironment. Their purpose was to verify immune system involvement in cancer growth and progression, highlighting the differences in immune infiltrate among tumor histotypes. More recently, some authors have provided a more comprehensive view of the relationships between tumor and immune system involved in thyroid carcinogenesis. The Cancer Genome Atlas (TCGA) delivered a large amount of data that allowed to combine information on the inflammatory microenvironment with gene expression data, genetic and clinical-pathological characteristics, and differentiation degree of papillary thyroid carcinoma (PTC). Moreover, using a new sensitive and highly multiplex analysis, the NanoString Technology, it was possible to divide thyroid tumors in two main clusters based on expression of immune-related genes. Starting from these results, the authors performed an immune phenotype analysis that allowed to classify thyroid cancers in hot, cold, or intermediate depending on immune infiltration patterns of the tumor microenvironment. The aim of this review is to provide a comprehensive and updated view of the knowledge on immune landscape of thyroid tumors. Understanding interactions between tumor and microenvironment is crucial to effectively direct immunotherapeutic approaches in the treatment of thyroid cancer, particularly for those not responsive to conventional therapies.
Highlights
Tumorigenesis is a multistep process that allows proliferation of mutated cells and development of neoplastic mass
Findings of a direct correlation between RET/PTC3 and IDO1 and between BRAFV600E and PD-L1 suggest that different driver mutations associated with different subtype of thyroid cancer contribute to different microenvironments and differential recruitment of cells to thyroid tumors
The Cancer Genome Atlas (TCGA), a study that described the genomic landscape of 496 papillary thyroid carcinoma (PTC), was the first work to suggest the usefulness of alternative classifications alongside that based on histological characteristics
Summary
Tumorigenesis is a multistep process that allows proliferation of mutated cells and development of neoplastic mass. Solid tumors are a heterogeneous population of different cell types including cancer cells, cancer stem cells, stromal cells (such as fibroblasts, mesenchymal stromal cells, endothelial cells, pericytes) and immune cells [such as T and B lymphocytes, natural killer cells (NKs) and tumor-associated macrophages (TAMs)] These cells, the produced molecules (such as cytokines, chemokines, enzymes, and other soluble factors) and the extracellular matrix constitute the tumor microenvironment (TME). The first stage of immunoediting, transformed cells that accumulate gene mutations in gatekeepers or caretakers and express aberrant antigens on their surface, are recognized and eliminated by the immune system. This phenomenon can lead to the selection of those cells that have developed strategies to escape immune survaillance. The further and progressive accumulation of genetic mutations and modification in the TME allow the tumor to evade completely immune response
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
