CC BY-NC-ND 4.0 · Laryngorhinootologie 2021; 100(S 02): S122-S123
DOI: 10.1055/s-0041-1727963
Abstracts
Head-Neck-Oncology: HPV / Tumor Marker

RNA-sequencing reveals an immune “hot” gene expression signature in oropharyngeal squamous cell carcinoma which is upregulated upon decitabine treatment in cell lines

J Ezic
1   Ulm University Medical Center, Department of Otorhinolaryngology and Head & Neck Surgery, Ulm
,
A von Witzleben
1   Ulm University Medical Center, Department of Otorhinolaryngology and Head & Neck Surgery, Ulm
,
A Fehn
1   Ulm University Medical Center, Department of Otorhinolaryngology and Head & Neck Surgery, Ulm
,
M Bens
3   Leibniz Institute on Aging - Fritz Lipmann Institute, Jena
,
J Thomas
2   Faculty of Medicine, Cancer Sciences Unit, Southampton, United Kingdom
,
O Ammerpohl
4   Ulm University Medical Center, Institute for Human Genetics, Ulm
,
J Kolarova
4   Ulm University Medical Center, Institute for Human Genetics, Ulm
,
H Kestler
5   Ulm University, Institute for Medical Systems Biology, Ulm
,
J Kraus
5   Ulm University, Institute for Medical Systems Biology, Ulm
,
J Döscher
1   Ulm University Medical Center, Department of Otorhinolaryngology and Head & Neck Surgery, Ulm
,
P Schuler
1   Ulm University Medical Center, Department of Otorhinolaryngology and Head & Neck Surgery, Ulm
,
J Greve
1   Ulm University Medical Center, Department of Otorhinolaryngology and Head & Neck Surgery, Ulm
,
R Marienfeld
6   Ulm University Medical Center, Institute for Pathology, Ulm
,
T Barth
6   Ulm University Medical Center, Institute for Pathology, Ulm
,
P Möller
6   Ulm University Medical Center, Institute for Pathology, Ulm
,
A Kleger
7   Ulm University Medical Center, Department of Internal Medicine I, Ulm
,
M-N Theodoraki
1   Ulm University Medical Center, Department of Otorhinolaryngology and Head & Neck Surgery, Ulm
,
M Brand
1   Ulm University Medical Center, Department of Otorhinolaryngology and Head & Neck Surgery, Ulm
,
C Brunner
1   Ulm University Medical Center, Department of Otorhinolaryngology and Head & Neck Surgery, Ulm
,
T Hoffmann
1   Ulm University Medical Center, Department of Otorhinolaryngology and Head & Neck Surgery, Ulm
,
C Ottensmeier
2   Faculty of Medicine, Cancer Sciences Unit, Southampton, United Kingdom
,
S Laban
1   Ulm University Medical Center, Department of Otorhinolaryngology and Head & Neck Surgery, Ulm
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    Content Introduction A significant percentage of oropharyngeal squamous cell carcinoma (OPSCC) is human papillomavirus (HPV) driven. HPV-positive OPSCC have a prognostic advantage likely due to cancer-specific immunity. We aimed to identify expression patterns of immune-related genes to assign “hot”and “cold” tumors.

    Material and Methods RNA sequencing was performed in 51 patients (Cohort 1, HPV-: n=19, HPV+: n=32), and in 6 HNSCC cell lines (HPV-: n=3, HPV+: n=3). Cell lines were treated with 2µM decitabine (DAC) or control-treated (DMSO). A validation cohort was obtained from The Cancer Genome Atlas (TCGA, Cohort 2, HPV-: n=18, HPV+: n=48). Differential gene expression analysis was performed using deseq2 (1.29.16), and gene ontology using clusterProfiler (3.18.0) R packages.

    Results An immune signature (n=32 genes) was developed based on the comparison of CD8high/low and CD103high/low tumors in Cohort 1 and validated in cohort 2. The signature was cross-validated and refined using a previously established signature to define “hot”and “cold” tumors resulting in a 47 gene immune signature. Differential gene expression analysis confirmed an upregulation of immune-related genes in “hot”tumors (n=428 genes). That gene set was further analyzed in HNSCC cell lines +/- DAC treatment. Differential gene expression analysis showed that DAC treatment leads to an increase of immune-related gene expression in-vitro, which was confirmed by gene ontology analysis.

    Conclusions Based on our findings, it seems that DAC treatment causes an increase in expression of immune-relate genes which could lead to increased tumor immunogenicity and may enhance immunotherapy results.

    Poster-PDF A-1581.pdf


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    Conflict of interest

    The first author points out the following conflict of interest: Simon Laban: Advisory Boards: Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Astra Zeneca (AZ). Honoraria: MSD, BMS, AZ, Merck Serono.Johannes Döscher: Advisory Boards: Merck Serono. MSD. Honoraria: Merck Serono.Patrick J. Schuler: Advisory Boards: BMS, MSD.Thomas K. Hoffmann: Advisory Boards: MSD, BMS. Honoraria: MSD, BMS, Merck Serono.All other authors declared no conflict of interests.

    Address for correspondence

    Ezic Jasmin
    Ulm University Medical Center, Department of Otorhinolaryngology and Head & Neck Surgery
    Frauensteige 14a
    89075 Ulm

    Publikationsverlauf

    Artikel online veröffentlicht:
    13. Mai 2021

    © 2021. 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/).

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