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

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Abstract

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.

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Author notes

  1. These authors contributed equally: Silvia Cantara, Eugenio Bertelli

Authors and Affiliations

  1. Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy

    Silvia Cantara, Lucia Brilli, Furio Pacini & Maria Grazia Castagna

  2. Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy

    Eugenio Bertelli & Marì Regoli

  3. Unit of Pathology, Arezzo Hospital, Arezzo, Italy

    Rossella Occhini

  4. University of Siena, Siena, Italy

    Paolo Toti

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  1. Silvia Cantara
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Correspondence to Silvia Cantara.

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Cantara, S., Bertelli, E., Occhini, R. et al. Blockade of the programmed death ligand 1 (PD-L1) as potential therapy for anaplastic thyroid cancer. Endocrine 64, 122–129 (2019). https://doi.org/10.1007/s12020-019-01865-5

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  • DOI: https://doi.org/10.1007/s12020-019-01865-5

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