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Adam, Pia [Author]; Kircher, Stefan [Author]; Sbiera, Iuliu [Author]; Koehler, Viktoria Florentine [Author]; Berg, Elke [Author]; Knösel, Thomas [Author]; Sandner, Benjamin [Author]; Fenske, Wiebke Kristin [Author]; Bläker, Hendrik [Author]; Smaxwil, Constantin [Author]; Zielke, Andreas [Author]; Sipos, Bence [Author]; Allelein, Stephanie [Author]; Schott, Matthias [Author]; Dierks, Christine [Author]; Spitzweg, Christine [Author]; Fassnacht, Martin [Author]; Kroiss, Matthias [Author]

FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale

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  • Media type: E-Article
  • Title: FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale
  • Contributor: Adam, Pia [Author]; Kircher, Stefan [Author]; Sbiera, Iuliu [Author]; Koehler, Viktoria Florentine [Author]; Berg, Elke [Author]; Knösel, Thomas [Author]; Sandner, Benjamin [Author]; Fenske, Wiebke Kristin [Author]; Bläker, Hendrik [Author]; Smaxwil, Constantin [Author]; Zielke, Andreas [Author]; Sipos, Bence [Author]; Allelein, Stephanie [Author]; Schott, Matthias [Author]; Dierks, Christine [Author]; Spitzweg, Christine [Author]; Fassnacht, Martin [Author]; Kroiss, Matthias [Author]
  • Published: Lausanne: Frontiers Research Foundation, [2023]
  • Published in: Frontiers in endocrinology ; 12, (2021)
  • Language: English
  • Keywords: FGFR ; immunotherapy ; immunohistochemistry ; PD-L1 ; tyrosine kinase inhibitor (TKI) ; immune checkpoint inhibitor (ICI)
  • Origination:
  • Footnote:
  • Description: Background: Treatment options for poorly differentiated (PDTC) and anaplastic (ATC)thyroid carcinoma are unsatisfactory and prognosis is generally poor. Lenvatinib (LEN), amulti-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 isapproved for advanced radioiodine refractory thyroid carcinoma, but response to singleagent is poor in ATC. Recent reports of combining LEN with PD-1 inhibitorpembrolizumab (PEM) are promising.Materials and Methods: Primary ATC (n=93) and PDTC (n=47) tissue samplesdiagnosed 1997-2019 at five German tertiary care centers were assessed for PD-L1expression by immunohistochemistry using Tumor Proportion Score (TPS). FGFR 1-4mRNA 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 FGFR1-4expression 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 asubgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFRexpression is low thyroid tumor cells. The clinically observed synergism of PEM withLEN may be caused by immune modulation.
  • Access State: Open Access
  • Rights information: Attribution (CC BY)