Programmed Death-Ligand 1 (PD-L1) Is a Potential Biomarker of Disease-Free Survival in Papillary Thyroid Carcinoma: a Systematic Review and Meta-Analysis of PD-L1 Immunoexpression in Follicular Epithelial Derived Thyroid Carcinoma

Girolami, Ilaria; Pantanowitz, Liron; Mete, Özgür; Brunelli, Matteo; Marletta, Stefano; Colato, Chiara; Trimboli, Pierpaolo; Crescenzi, Anna; Bongiovanni, Massimo; Barbareschi, M.; Eccher, Albino

doi:10.1007/s12022-020-09630-5

Cited by 45 publications

(38 citation statements)

References 56 publications

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“…A few studies reported the expression of PD-L1 in TCs. PD-L1 immunoexpression was found in 6.1 to 82.5% of PTCs (46,47), including cases of papillary thyroid microcarcinoma (48) and cases with simultaneous chronic thyroiditis and BRAF mutation (29,49). In PTCs a significant association between PD-L1 expression and BRAF V600E mutation has been reported in several studies (48,49).…”

Section: Discussionmentioning

confidence: 89%

“…The immunohistochemical expression of PD-L1 is sometimes a prerequisite for the establishment of checkpoint inhibitor therapy and has prognostic value in several types of malignant tumors (21,29). Based on the encouraging results of trials involving immunotherapy in the management of ATC (25), we have investigated PD-L1 expression and tumor microenvironment (TME) in a series of 15 ATCs and 13 PDTCs.…”

Section: Discussionmentioning

confidence: 99%

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PD‑L1 expression and immune cells in anaplastic carcinoma and poorly differentiated carcinoma of the human thyroid gland: A retrospective study

et al. 2021

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Anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid carcinoma (PDTC) have limited treatment options, and immune profiling may help select patients for immunotherapy. The prevalence and relevance of programmed death-1 ligand (PD-L1) expression and the presence of immune cells in ATC and PDTC has not yet been well established. The present study investigated PD-L1 expression (clone 22C3) and cells in the tumor microenvironment (TME), including tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs) and dendritic cells, in whole tissue sections of 15 cases of ATC and 13 cases of PDTC. Immunohistochemical PD-L1 expression using a tumor proportion score (TPS) with a 1% cut-off was detected in 9/15 (60%) of ATC cases and 1/13 (7.7%) of PDTC cases (P=0.006). PD-L1 expression in TILs was limited to the ATC group (73.3 vs. 0% in ATC and PDTC, respectively). In the ATC group, the TPS for tumor positive PD-L1 expression revealed a non-significant trend towards worse survival, but no difference was observed when investigating PD-L1 expression in TILs and TAMs. In addition to increased PD-L1 expression, all ATC cases exhibited significantly increased CD3 + and CD8 + T cells, CD68 + and CD163 + macrophages, and S100 + dendritic cells compared with the PDTC cases. Loss of mutL homolog 1 and PMS1 homolog 2 expression was observed in one ATC case with the highest PD-L1 expression, as well as in the only PDTC case positive for PD-L1. Notably, the latter was the only PDTC case exhibiting positivity for p53 and a cellular microenvironment similar to ATC. The current results indicated that PD-L1 expression was frequent in ATC, but rare in PDTC. In addition to PD-L1, the present study suggested that microsatellite instability may serve a role in both the TME and the identification of immunotherapy candidates among patients with PDTC.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

PD‑L1 expression and immune cells in anaplastic carcinoma and poorly differentiated carcinoma of the human thyroid gland: A retrospective study

et al. 2021

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“…PTC specimens with lymphoid thyroiditis showed higher expression of PD-L1 (39,1%) in comparison to PTC tissue without lymphoid thyroiditis (6,9%) ( 31 ). A review on the expression of PD-L1 in PTC tissue demonstrated significant association of PD-L1 expression with reduced disease-free survival (DFS), but not OS ( 32 ). We did not find any impact of PD-L1 expression on DSS.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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BackgroundTreatment 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 MethodsPrimary 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.ResultsPD-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.ConclusionHigh 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.

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“…The study's results indicated that PD-L1 expression was significantly associated with reduced disease-free survival, but no association was found with the overall survival. Besides, they found a significant association between PD-L1 expression in papillary thyroid carcinomas in terms of underlying chronic lymphocytic thyroiditis and BRAF V600E mutation status (21). Nevertheless, the knowledge of the relationship between PD-L1 and MTC is less than the tumors originating from follicular cells; only a few studies have evaluated PD-L1 positivity in MTC patients (22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

Pd-l1 expression in medullary thyroid carcinoma and its association with clinicopathological findings

Kemal¹,

Çalışkan²,

Gün³

et al. 2021

TJPATH

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Objective: Medullary thyroid carcinoma (MTC) is a rare tumor originating from parafollicular C cells. It has more aggressive biologic behavior than differentiated thyroid carcinomas, and it is insensitive to treatment with radioactive iodine. Vandetanib and cabozantinib are the newly approved tyrosine kinase inhibitors in advanced stages, but novel effective systemic therapeutics could be crucial and needed for the clinical management of these patients. We aimed to evaluate the Programmed death-ligand 1 (PD-L1) expression, which is a novel immunotherapy target, in our MTC cohort, and determine whether it has an association with clinical and pathological features. Material and Method:This retrospective study involved 41 cases of MTC with a median follow-up of 54 months. PD-L1 monoclonal antibody (SP263 clone) was investigated immunohistochemically. Complete and/or partial membranous staining pattern in more than 1% of tumor cells was considered positive. The correlations of PD-L1 expression with clinicopathologic and prognostic features were analyzed.Results: PD-L1 positivity was detected in 5 (12.2%) of 41 tumors. The extent of PD-L1 staining was low (<5%) for all tumors. There was no clinicopathologic and prognostic relevance regarding PD-L1 expression in our MTC patients. Conclusion:Although PD-L1 expression could be a potential biomarker to predict the prognosis of various cancers and response to checkpoint inhibitors, we did not find any significant correlation between PD-L1 expression and clinicopathologic features in our cases. Studies with larger patient numbers are still required to perform a more comprehensive analysis.

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Programmed Death-Ligand 1 (PD-L1) Is a Potential Biomarker of Disease-Free Survival in Papillary Thyroid Carcinoma: a Systematic Review and Meta-Analysis of PD-L1 Immunoexpression in Follicular Epithelial Derived Thyroid Carcinoma

Cited by 45 publications

References 56 publications

PD‑L1 expression and immune cells in anaplastic carcinoma and poorly differentiated carcinoma of the human thyroid gland: A retrospective study

PD‑L1 expression and immune cells in anaplastic carcinoma and poorly differentiated carcinoma of the human thyroid gland: A retrospective study

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

Pd-l1 expression in medullary thyroid carcinoma and its association with clinicopathological findings

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