Investigation of TIGIT methylation in head and neck squamous cell carcinomas

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.

Publikationsverlauf

Publikationsdatum:
23. April 2019 (online)