DNA methylation in tumour and normal mucosal tissue of head and neck squamous cell carcinoma (HNSCC) patients: new diagnostic approaches and treatment

2013 ◽  
Vol 30 (3) ◽  
Author(s):  
Nongnit Laytragoon-Lewin ◽  
Lars Erik Rutqvist ◽  
Freddi Lewin
2013 ◽  
Vol 19 (19) ◽  
pp. 5444-5455 ◽  
Author(s):  
Roberto A. Lleras ◽  
Richard V. Smith ◽  
Leslie R. Adrien ◽  
Nicolas F. Schlecht ◽  
Robert D. Burk ◽  
...  

Epigenetics ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. 398-409 ◽  
Author(s):  
Chongchang Zhou ◽  
Meng Ye ◽  
Shumin Ni ◽  
Qun Li ◽  
Dong Ye ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18527-e18527
Author(s):  
Angelika Martina Starzer ◽  
Gerwin Heller ◽  
Erwin Tomasich ◽  
Katharina Feldmann ◽  
Teresa Hatziioannou ◽  
...  

e18527 Background: Biomarkers for response prediction to immune checkpoint inhibitors in head and neck squamous cell carcinoma (HNSCC) patients are needed for a personalized therapy regimen. Therefore, we investigated the predictive potential of inflammatory biomarkers and DNA methylation. Methods: We profiled the methylation status of 850.000 CpG sites in formalin-fixed, paraffin-embedded primary HNSCC samples collected before ICI therapy start using Infinium Methylation EPIC microarrays. Tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1) expression were analyzed employing immunohistochemistry staining. Methylation profile, TIL density and PD-L1 expression were correlated with best radiological response to ICI treatment. Results: 29 patients (median age of 61; range 28-80) years; 8 (27.6%) females, 21 (72.4%) males) with HNSCC were included. Median number of prior systemic therapies was 1 (range 0-3). Median number of ICI applications was 6 (range 1-45). 2/29 (6.9%) patients achieved an objective response (complete response or partial response) under anti-PD-1 therapy. Median progression-free survival (PFS) and median overall survival (OS) were 3.3 months (range 0-28.8) and 7.2 months (range 0-29.4), respectively. 7/29 (24.1%) patients were still alive and one of these patients was still on ICI therapy at data cut-off. Methylation analyses revealed a combination of methylation changes (both hypo- and hypermethylation) that was predictive for response to ICI. 11/27 (40.7%) patients had PD-L1 expressing tumor cells ( > 1% PD-L1 expression). Median density of CD8+ TILs was 423.49 cells/mm2 tumor (range 5.71-11528.43 cells/mm2) and median density of CD3+ TILs was 794.82 cells/mm2 tumor (range 1.68-8811.74 cells/mm2). There was no correlation of PD-L1 expression, density of CD8+ or CD3+ TILs with response or disease control (p > 0.05). Conclusions: In contrast to PD-L1 expression and TIL density, methylation profiles were associated with response to ICI treatment in HNSCC patients.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Andrey Finegersh ◽  
Scott Kulich ◽  
Theresa Guo ◽  
Alexander V. Favorov ◽  
Elana J. Fertig ◽  
...  

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