Blockade of the programmed death ligand 1 (PD-L1) as potential therapy for anaplastic thyroid cancer

• Published in: Endocrine Vol. 64; no. 1; pp. 122 - 129
• Main Authors: Cantara, Silvia, Bertelli, Eugenio, Occhini, Rossella, Regoli, Marì, Brilli, Lucia, Pacini, Furio, Castagna, Maria Grazia, Toti, Paolo
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2019; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Animal models; Animals; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen - antagonists & inhibitors; Cancer immunotherapy; Cancer therapies; Cell Line, Tumor; Clinical trials; Diabetes; Endocrinology; Endothelium; Female; Humanities and Social Sciences; Humans; Immunotherapy; Internal Medicine; Male; Medicine; Medicine & Public Health; Mice; Middle Aged; Monoclonal antibodies; multidisciplinary; Oncology; Original Article; PD-1 protein; PD-L1 protein; Protein-tyrosine kinase; Radiation therapy; Science; Thyroid cancer; Thyroid carcinoma; Thyroid Carcinoma, Anaplastic - drug therapy; Thyroid Carcinoma, Anaplastic - pathology; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - pathology; Treatment Outcome; Tumors; PD-L1; Anaplastic thyroid cancer; PD-1; Immunotherapy
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-019-01865-5

Purpose Anaplastic thyroid carcinoma (ATC) is a rare, highly aggressive form of thyroid cancer (TC) characterized by an aggressive behavior and poor prognosis, resulting in patients’ death within a year. Standard treatments, such as chemo and radiotherapy, as well as tyrosine kinase inhibitors, are ineffective for ATC treatment. Cancer immunotherapy is one of the most promising research area in oncology. The PD-1/PD-L1 axis is of particular interest, in light of promising data showing a restoration of host immunity against tumors, with the prospect of long-lasting remissions. Methods In this study, we evaluated PD-L1 expression in a large series of TCs (20 cases) showing a progressive dedifferentiation of the thyroid tumor from well differentiated TC to ATC, employing two different antibodies [R&D Systems and VENTANA PD-L1 (SP263) Rabbit Monoclonal Primary Antibody]. We also tested the anti PD-L1 mAb in an in vivo animal model. Results We found that approximately 70–90% of ATC cases were positive for PD-L1 whereas normal thyroid and differentiated TC were negative. Moreover, all analyzed cases presented immunopositive staining in the endothelium of vessels within or in close proximity to the tumor, while normal thyroid vessels were negative. PD-L1 mAb was also effective in inhibiting ATC growth in an in vivo model. Conclusions These data suggest that immunotherapy may be a promising treatment specific for ATC suggesting the need to start with clinical TRIALs.