Wnt/B-catenin activation and TP53 mutations associate with distinct immune profiles in advanced thyroid cancer.

Context: Anaplastic thyroid carcinomas (ATCs) and poorly differentiated thyroid carcinomas (PDTCs) exhibit distinct immune-related gene expression profiles. Most ATCs are characterized by active immune interactions (hot or altered immunosuppressed immunophenotypes), while PDTCs are largely immunologically inert (cold immunophenotypes).

Objective: This study aimed to elucidate the mechanisms driving these divergent immunological fates, focusing on the Wnt/β-catenin pathway and TP53 mutations.

Immune Landscape of Thyroid Cancers: New Insights.

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 and studies showed that thyroid tumor cells can avoid immune response by promoting an immunosuppressive microenvironment.

THERAPY OF ENDOCRINE DISEASE Immunotherapy of advanced thyroid cancer: from bench to bedside.

Immunotherapy has arisen in use in the field of oncology with seven immune checkpoint inhibitors approved for the treatment of a variety of cancer histologies. Depending on the cancer type, the success rate might be different, but in average it is about 20%, with some cases showing a durable response, lasting also after the interruption of the treatment, with a clear benefit on OS. The development of an efficacious cure for advanced thyroid carcinomas is still an unmet need and immunotherapy represents an interesting alternative option also for this cancer.

The Aryl Hydrocarbon Receptor Is Expressed in Thyroid Carcinoma and Appears to Mediate Epithelial-Mesenchymal-Transition.

Aryl hydrocarbon receptor (AhR) is expected to promote initiation, progression and invasion of cancer cells regulating proliferation, differentiation, gene expression, inflammation, cell motility and migration. Furthermore, an immunosuppressant function of AhR has been recognized. This study evaluated AhR expression and its role in thyroid cancer progression.

Immune Profiling of Thyroid Carcinomas Suggests the Existence of Two Major Phenotypes: An ATC-Like and a PDTC-Like.

Objectives: The understanding of the mechanisms underlying thyroid cancer immune escape can lead to the identification of new molecular targets and/or efficacy biomarkers. For this purpose, we performed immune expression profiling in thyroid cancers to obtain a comprehensive view on immune mechanisms activated during cancer progression.

Methods: The study was conducted retrospectively in 25 papillary thyroid carcinomas (PTCs), 14 poorly differentiated thyroid carcinomas (PDTC), 13 anaplastic thyroid carcinomas (ATCs), and 7 normal thyroid (NT) tissue samples.

Signal Transducer and Activator of Transcription 1 Plays a Pivotal Role in RET/PTC3 Oncogene-induced Expression of Indoleamine 2,3-Dioxygenase 1.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a single chain oxidoreductase that catalyzes tryptophan degradation to kynurenine. In cancer, it exerts an immunosuppressive function as part of an acquired mechanism of immune escape. Recently, we demonstrated that IDO1 expression is significantly higher in all thyroid cancer histotypes compared with normal thyroid and that its expression levels correlate with T regulatory (Treg) lymphocyte densities in the tumor microenvironment.

Timing of breakfast does not influence therapeutic efficacy of liquid levothyroxine formulation.

Oral levothyroxine (L-T4) is the mainstay of hypothyroidism treatment. Many factors may influence its absorption, including the timing of administration. Objective of the study is to demonstrate the therapeutic equivalence of administering liquid L-T4 with breakfast or 10 min before breakfast.

Indoleamine 2,3-dioxygenase 1 (IDO1) is up-regulated in thyroid carcinoma and drives the development of an immunosuppressant tumor microenvironment.

Context: Indoleamine 2,3-dioxygenase 1 (IDO1) is a single chain oxidoreductase that catalyzes tryptophan degradation to kynurenine. In cancer, it appears to exert an immunosuppressive function as part of an acquired mechanism of immune escape mediated by the inhibition of lymphocyte proliferation and survival and by the induction of FoxP3+ T regulatory cells.

Objective: The objective of the study was to evaluate IDO1 expression in thyroid carcinoma and demonstrate its immunosuppressive function in the context of thyroid tumors.

Intracellular signal transduction and modification of the tumor microenvironment induced by RET/PTCs in papillary thyroid carcinoma.

RET gene rearrangements (RET/PTCs) represent together with BRAF point mutations the two major groups of mutations involved in papillary thyroid carcinoma (PTC) initiation and progression. In this review, we will examine the mechanisms involved in RET/PTC-induced thyroid cell transformation. In detail, we will summarize the data on the molecular mechanisms involved in RET/PTC formation and in its function as a dominant oncogene, on the activated signal transduction pathways and on the induced gene expression modifications.