We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale.
- Authors
Adam, Pia; Kircher, Stefan; Sbiera, Iuliu; Koehler, Viktoria Florentine; Berg, Elke; Knösel, Thomas; Sandner, Benjamin; Fenske, Wiebke Kristin; Bläker, Hendrik; Smaxwil, Constantin; Zielke, Andreas; Sipos, Bence; Allelein, Stephanie; Schott, Matthias; Dierks, Christine; Spitzweg, Christine; Fassnacht, Martin; Kroiss, Matthias
- Abstract
Background: Treatment options for poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinoma are unsatisfactory and prognosis is generally poor. Lenvatinib (LEN), a multi-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 is approved for advanced radioiodine refractory thyroid carcinoma, but response to single agent is poor in ATC. Recent reports of combining LEN with PD-1 inhibitor pembrolizumab (PEM) are promising. Materials and Methods: Primary ATC (n=93) and PDTC (n=47) tissue samples diagnosed 1997-2019 at five German tertiary care centers were assessed for PD-L1 expression by immunohistochemistry using Tumor Proportion Score (TPS). FGFR 1-4 mRNA was quantified in 31 ATC and 14 PDTC with RNAscope in-situ hybridization. Normal thyroid tissue (NT) and papillary thyroid carcinoma (PTC) served as controls. Disease specific survival (DSS) was the primary outcome variable. Results: PD-L1 TPS≥50% was observed in 42% of ATC and 26% of PDTC specimens. Mean PD-L1 expression was significantly higher in ATC (TPS 30%) than in PDTC (5%; p<0.01) and NT (0%, p<0.001). 53% of PDTC samples had PD-L1 expression ≤5%. FGFR mRNA expression was generally low in all samples but combined FGFR1-4 expression was significantly higher in PDTC and ATC compared to NT (each p<0.001). No impact of PD-L1 and FGFR 1-4 expression was observed on DSS. Conclusion: High tumoral expression of PD-L1 in a large proportion of ATCs and a subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR expression is low thyroid tumor cells. The clinically observed synergism of PEM with LEN may be caused by immune modulation.
- Subjects
IODINE isotopes; THYROID cancer; FIBROBLAST growth factor receptors; PROGRAMMED death-ligand 1; IMMUNE checkpoint inhibitors
- Publication
Frontiers in Endocrinology, 2021, Vol 12, p1
- ISSN
1664-2392
- Publication type
Article
- DOI
10.3389/fendo.2021.712107