CC BY-NC-ND 4.0 · Laryngorhinootologie 2020; 99(S 02): S162
DOI: 10.1055/s-0040-1711022
Abstracts
Oncology

Abundance of immune checkpoint molecules and their ligands in Oropharyngeal Squamous cell carcinoma (OPSCC) depends on HPV status and can be modulated by demethylation.

A Fehn
1   Klinik für HNO & Kopf-Hals-Chirurgie Universitätsklinikum Ulm, Forschungslabor Ulm
,
J Ezic
1   Klinik für HNO & Kopf-Hals-Chirurgie Universitätsklinikum Ulm, Forschungslabor Ulm
,
C Brunner
1   Klinik für HNO & Kopf-Hals-Chirurgie Universitätsklinikum Ulm, Forschungslabor Ulm
,
Marie-Nicole Theodoraki
2   Klinik für HNO & Kopf-Hals-Chirurgie Universitätsklinikum Ulm Ulm
,
J Döscher
2   Klinik für HNO & Kopf-Hals-Chirurgie Universitätsklinikum Ulm Ulm
,
P Schuler
2   Klinik für HNO & Kopf-Hals-Chirurgie Universitätsklinikum Ulm Ulm
,
J Greve
2   Klinik für HNO & Kopf-Hals-Chirurgie Universitätsklinikum Ulm Ulm
,
R Marienfeld
3   Institut für Pathologie Universiätsklinikum Ulm Ulm
,
K Koretz
3   Institut für Pathologie Universiätsklinikum Ulm Ulm
,
T Hoffmann
2   Klinik für HNO & Kopf-Hals-Chirurgie Universitätsklinikum Ulm Ulm
,
S Laban
2   Klinik für HNO & Kopf-Hals-Chirurgie Universitätsklinikum Ulm Ulm
› Author Affiliations
 
 

    Introduction Immune checkpoint molecules (ICM) regulate immune cell functions and anti-cancer immunity. ICM expression within the tumor microenvironment (TME) may differ by HPV-status. Decitabine (DAC), a nucleoside analogue, causes unspecific DNA demethylation resulting in increased expression of cancer testis antigens, potentially enhancing immunogenicity. Systemic DAC may also impact immune cells in the microenvironment and the periphery. Here, we aim at characterizing ICM expression in the TME and effects of DAC on ICM ligands in cancer cells.

    Material & Methods RNA of 13 HPV+ and 12 HPV- OPSCC was extracted. Whole exome sequencing of RNA was performed (40 Mio reads). In addition, RNA from three HPV+ (UD-SCC-2, UM-SCC-47, UPCI-SCC:90) and three HPV- OPSCC cell-lines (UD-SCC-1, UD-SCC-4, UD-SCC-5) was extracted after treatment with DAC (2µmol/l) or control (DMSO) for five consecutive Days. Expression data of ICM and their ligands were compared using Mann-Whitney U test (OPSCC samples by HPV-status) or paired Wilcoxon signed rank test (cell lines).

    Results ICM ligand expression in the TME was significantly altered for PVR (p<0.001), ICOSL, Galectin-9 and IGSF11 (p<0.05). After DAC treatment, the following ICM ligands with inhibitory or stimulatory potential showed increased expression: PD-L1, CEACAM1, PVRL2, PVR, TNFRSF14, 4-1BBL, CD27L, GITRL (p<0.05).

    Discussion Expression of ICM and their ligands in the TME tends to be higher in HPV-positive OPSCC indicating an inflamed phenotype. DAC affects both, the expression of stimulatory and inhibitory ICM ligands in cancer cell lines. The functional impact of these effects needs to be analyzed further.

    Poster-PDF A-1909.PDF


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    Adrian Fehn
    Klinik für HNO & Kopf-Hals-Chirurgie Universitätsklinikum Ulm, Forschungslabor
    Frauensteige 12
    89075 Ulm

    Publication History

    Article published online:
    10 June 2020

    © 2020. 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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