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

Salvatore Ulisse,Alessandro Antonelli,Nicola Cornacchini,Giovanni Carbotta,Massimo Monti,Maria Amabile,Alessio Metere,Francesco Tartaglia,Laura Giacomelli,Chiara Tuccilli,Massimo Vergine,Eleonora D’Armiento,Daniele Pironi,Poupak Fallahi,Antonio Catania,Enke Baldini,Salvatore Sorrenti

doi:10.3390/ijms20061405

Abstract

The new immunotherapy targeting the programmed cell death 1 (PD-1) receptor and its cognate ligand PD-L1 has renewed hopes of eradicating the most difficult human cancers to treat. Among these, there are the poorly differentiated and anaplastic thyroid cancers, unresponsive to all the therapies currently in use. In the present review we will summarize information regarding the expression of PD-L1 in the different thyroid cancer histotypes, its correlation with clinicopathological features, and its potential prognostic value. Then, we will evaluate the available data indicating the PD-1/PD-L1 axis as a promising target for thyroid cancer therapy.

Highlights

Thyroid cancer represents the most common endocrine malignancy and the fifth most common cancer in women in the United States [1]
In the case of indeterminate atypia or follicular proliferation, fine-needle aspiration cytology (FNAC) fails to discriminate adenomas from follicular thyroid carcinoma (FTC) or follicular variants of papillary thyroid carcinoma (PTC) (FVPTC), which implies the overtreatment of many patients subjected to unnecessary thyroid resection
The authors found no significant differences in PD-L1 cytoplasmic staining between NIFTP and thyroid benign lesions, while a considerable increase was observed between NIFTP or benign lesion and invasive FVPTC [69,70,71]

Summary

Thyroid Cancer

Thyroid cancer represents the most common endocrine malignancy and the fifth most common cancer in women in the United States [1]. The same multigene panels used to detect tumor-associated genetic alterations in thyroid FNA, like ThyroSeq, are able to categorize a small subset of thyroid cancers with the most unfavorable outcomes, providing cancer risk stratification even before surgery [12]. This novel approach is promising, it needs extensive validation on large case studies and integration with clinical parameters of prognostic relevance. External beam radiation and chemotherapy do not elicit effective therapeutic responses, and new therapeutic strategies aimed at eradicating aggressive thyroid tumors are urgently needed [7,17,20,21,22,23]

Dysregulation of the Immune System in Thyroid Cancer

Expression and Clinical Utility of PD-1 Ligands in Thyroid Cancer

PD-L1 Expression and Thyroid Cancer Diagnosis

PD-1 Ligand Expression and Thyroid Cancer Prognosis

Findings

Conclusions