CC BY-NC-ND 4.0 · Laryngorhinootologie 2019; 98(S 02): S85
DOI: 10.1055/s-0039-1686090
Abstracts
Oncology

Investigation of TIGIT methylation in head and neck squamous cell carcinomas

TJ Vogt
1   Klinik für Hals-Nasen-Ohrenheilkunde Universität Bonn, Bonn
,
A Franzen
2   HNO Uniklinikum Bonn, Bonn
,
F Bootz
2   HNO Uniklinikum Bonn, Bonn
,
D Dietrich
2   HNO Uniklinikum Bonn, Bonn
› Author Affiliations
› Further Information
Also available at
 
 

    Introduction:

    Immunotherapy is a promising treatment for head and neck squamous cell carcinomas (HNSCC) patients. TIGIT (T cell immunoreceptor with Ig and ITIM domains) is a promising target for a novel immune checkpoint inhibition. Therefore, this study aimed at investigating DNA methylation of TIGIT with regard to mRNA expression, molecular features, immune cell infiltrates and outcome of HNSCC patients.

    Material:

    Molecular and clinico-pathological data of N = 528 HNSCC patients were obtained from The Cancer Genome Atlas. Methylation was determined within the transscription start site of TIGIT. Additionaly, isolated immune cells of healthy individuals and tumor cell lines were analyzed.

    Results:

    TIGIT was significantly lower methylated in tumor tissue compared to normal adjacent tissue (tumor: 84.2%, normal: 90.7%, P < 0.001). In tumor tissues, significant inverse correlations of methylation with mRNA expression (Spearman's ρ=-0.446, P < 0.001) as well as immune cell infiltrates (CD8 T cells ρ=-0.402, P < 0.001) were observed. A significantly higher methylation level within TIGIT was detected in HNSCC cell lines (81.7%) compared to isolated immune cells (CD8 T cells: 60.6%; CD4 T cells: 68.8%; Treg cells: 35.4%; for each comparison P < 0.001).

    Conclusion:

    Our results point towards an epigentic regulation of TIGIT via DNA methylation and might open a new avenue fot the development of predictive biomarkers for the response to anti-TIGIT immune checkpoint blockade.


    #
    Timo Jakob Vogt
    Uniklinik Bonn,
    Adenauerallee 64, 53113
    Bonn

    Publication History

    Publication Date:
    23 April 2019 (online)

    © 2019. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

    Georg Thieme Verlag KG
    Stuttgart · New York