In a Novel Malignant Pleural Effusion Derived Anaplastic Thyroid Cancer Line PD-L1 Expression is Strongly Increased by HDAC Inhibitor Treatment

Anaplastic thyroid cancer is a deadly disease causing around 30% of thyroid cancer related death. Beside surgery pre- and postoperative radiotherapy and chemotherapy can be offered as treatment for patients and for metastatic or unresectable ATC with BRAFV600E mutation recently BRAF and MEK inhibitor combined treatment was approved by the FDA. However further preclinical models and novel combinations are necessary to improve patient survival. We established a new anaplastic thyroid cancer cell line from the pleural effusion sample of a 69 year old male patient. The cells carry mutations in their BRAF gene (V660E) and their TERT promoter region and showed positivity for PAX8 staining. We found that the cells have strong migratory activity in vitro and highly metastatic in vivo. After intrapleural injection in immunocompromised mice within two weeks widespread pleural carcinosis developed and the cells invaded the lung, the skeletal muscle and the heart. Combined treatment with BRAF and MEK inhibitors reduced the proliferation of the cells and significantly inhibited cell migration. Treatment with histone deacetylase (HDAC) inhibitors initiated cell cycle arrest in the G2/M phase and strongly induced PD-L1 expression of the cells. Paclitaxel-cisplatin chemotherapeutic treatment could reduce the viability of the cells but it alone did not increased PD-L1 expression. However in combination with HDAC inhibitor treatment the elevation of PD-L1 expression was also present. Similar results was obtained with anaplastic thyroid cancer cell line BTH-101, PD-L1 expression was strongly increased by HDAC inhibitor treatment in these cell both alone and in combination with paclitaxel-cisplatin treatment. Our results show that combination of standard chemotherapy with HDAC inhibition influences immune checkpoint protein expression and thus may impact the response to immunotherapy.