TY  - JOUR
A1  - Adam, Pia
A1  - Kircher, Stefan
A1  - Sbiera, Iuliu
A1  - Koehler, Viktoria Florentine
A1  - Berg, Elke
A1  - Knösel, Thomas
A1  - Sandner, Benjamin
A1  - Fenske, Wiebke Kristin
A1  - Bläker, Hendrik
A1  - Smaxwil, Constantin
A1  - Zielke, Andreas
A1  - Sipos, Bence
A1  - Allelein, Stephanie
A1  - Schott, Matthias
A1  - Dierks, Christine
A1  - Spitzweg, Christine
A1  - Fassnacht, Martin
A1  - Kroiss, Matthias
T1  - FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale
T2  - Frontiers in Endocrinology
N2  - 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.
KW  - tyrosine kinase inhibitor (TKI)
KW  - immune checkpoint inhibitor (ICI)
KW  - immunohistochemistry
KW  - immunotherapy
KW  - PD-L1
KW  - FGFR
Y1  - 2021
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/24465
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-244653
SN  - 1664-2392
VL  - 12
ER  -