HDAC Inhibition Induces PD-L1 Expression in a Novel Anaplastic Thyroid Cancer Cell Line.

Abstract

While papillary thyroid cancer (PTC) has largely favorable prognosis, anaplastic thyroid cancer (ATC) is a rare but extremely aggressive malignancy with grim clinical outcome. Even though new therapeutic options are emerging for ATC, additional preclinical models and novel combinations are needed for specific subsets of patients. We established a novel cell line (PF49) from the malignant pleural effusion of a 68-year-old male patient with ATC that rapidly transformed from a BRAF and TERT promoter mutant PTC. PF49 cells demonstrated a robust migratory activity in vitro and strong invasive capacity in vivo in a pleural carcinosis model. Combined BRAF and MEK inhibition decreased the proliferation and migration of PF49 cells, however could not induce cell death. Importantly, HDAC inhibitor treatment with SAHA or valproic acid induced cell cycle arrest and strongly increased PD-L1 expression of the tumor cells. Induction of PD-L1 expression was also present when paclitaxel-cisplatin chemotherapeutic treatment was combined with HDAC inhibitor treatment. Increased PD-L1 expression after HDAC inhibition was recapitulated in an international ATC cell model. Our data suggest that HDAC inhibition alone or in combination with standard chemotherapy may potentiate anaplastic thyroid cancer cells for immunotherapy.

• Authors: Luca Hegedűs, Dominika Rittler, Tamás Garay, Paul Stockhammer, Ildikó Kovács, Balázs Döme, Sarah Theurer, Thomas Hager, Thomas Herold, Stavros Kalbourtzis, Agnes Bankfalvi, Kurt W Schmid, Dagmar Führer, Clemens Aigner, Balázs Hegedűs
• Journal: Pathology oncology research : POR (Pathol Oncol Res) Vol. 26 Issue 4 Pg. 2523-2535 (Oct 2020) ISSN: 1532-2807 [Electronic] Switzerland
• PMID: 32591993 (Publication Type: Case Reports, Journal Article)

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• Histone Deacetylase Inhibitors

Topics

• Aged
• Animals
• B7-H1 Antigen (biosynthesis, drug effects)
• Cell Line, Tumor (drug effects, metabolism)
• Cell Transformation, Neoplastic (pathology)
• Histone Deacetylase Inhibitors (pharmacology)
• Humans
• Male
• Mice
• Mice, SCID
• Thyroid Cancer, Papillary (pathology)
• Thyroid Carcinoma, Anaplastic (metabolism, pathology)
• Thyroid Neoplasms (metabolism, pathology)
• Xenograft Model Antitumor Assays