Recent advances in understanding immune phenotypes of thyroid carcinomas: prognostication and emerging therapies

Abstract

Tumors modulate the host immune cells within their microenvironment to avoid recognition and elimination by our immune system, a phenotype called cancer immune escape. Different mechanisms responsible for cancer immune escape that result either in decreased tumor immunogenicity or in increased tumor immunosuppressive activity have been identified. Recently, various immunotherapeutic approaches have been developed with the aim to revert tumor immune escape. The aims of this review are to explore the immunological aspects of thyroid cancer and to assess whether these features can be exploited in the prognosis and treatment of advanced forms of this disease. Therefore, we will describe the immune landscape and phenotypes of thyroid cancer, summarize studies investigating the expression of immunomodulatory molecules, and finally describe the preclinical and clinical trials investigating the utility of immunotherapies in the management of thyroid cancer. The aim of this review is to explore the immunological aspects of thyroid cancer and to assess whether these features can be exploited in the prognosis and treatment of advanced forms of this disease. Therefore, we will describe the immune-landscape and phenotypes of thyroid cancer, we will summarize studies investigating the expression of immunomodulatory molecules, and we will finally describe the preclinical and clinical trials investigating the utility of immunotherapies in the management of thyroid cancer.

Mechanisms of the Impact of Hashimoto Thyroiditis on Papillary Thyroid Carcinoma Progression: Relationship with the Tumor Immune Microenvironment

“…Previous studies have shown that elevation of Treg cells in primary tumors is associated with metastasis and poor prognosis [30]. These cells facilitate tumor immune escape by producing cytokines (IL-10, transforming growth factor-β, and IL-35) and by inhibiting T-cell receptor activation [31]. However, in our study, we found that most patients with PTC had few Treg cells.…”

“…Classically activated M1-like macrophages are able to kill tumor cells directly through an early elimination phase of immuno-editing orchestrated by CD8+ cytotoxic T lymphocytes and interferons [ 33 ]. However, M2 macrophages are much more abundant in malignancies [ 31 ]. The presence of these cells correlates with angiogenesis, immunosuppression, and the promotion of cancer growth and metastasis [ 34 ].…”

PD-1 Ligand Expression in Epithelial Thyroid Cancers: Potential Clinical Implications

“…WDTCs are supposed to be poorly immunogenic because of their low mutational burden due to low neoantigen expression [33]. However, they are infiltrated by several host immune cells, including NK, tumor-associated macrophages, mast cells, dendritic cells, B and T lymphocytes [34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51].…”

PD-1 Blockade Delays Tumor Growth by Inhibiting an Intrinsic SHP2/Ras/MAPK Signalling in Thyroid Cancer Cells

“…The evaluation of PD-1 expression in cancer cell might be important to identify tumours and/or patients that will be likely to respond to ICI administration by taking advantage of both drug effects on immune compartment and on cancer cell proliferation. In few case reports or in "basket clinical trials" in which ICI [i.e., Pembrolizumab (anti-PD-1), Nivolumab (anti-PD-1), or Atezolizumab (anti-PD-L1)] were used alone or in combination with Multikinase Inhibitors (MKI) for the treatment of advanced and/or metastatic TC, encouraging preliminary clinic evidence of e cacy has been reported [9,50,51].…”