Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-9604
Authors: | Zahnreich, Sebastian El Guerzyfy, Soumia Kaufmann, Justus Schmidberger, Heinz |
Title: | The cGAS/STING/IFN-1 response in squamous head and neck cancer cells after genotoxic challenges and abrogation of the ATR-Chk1 and Fanconi anemia axis |
Online publication date: | 21-Nov-2023 |
Year of first publication: | 2023 |
Language: | english |
Abstract: | Locally advanced head and neck squamous cell carcinomas (HNSCC) are often refractory to platinum-based radiochemotherapy and new immuno-oncological strategies. To stimulate immunogenic antitumor responses in HNSCC patients, we investigated the cGAS/STING/IFN-1 signaling pathway after genotoxic treatments and concomitant abrogation of the DNA damage response (DDR). For this purpose, FaDu and UM-SCC1 cells were exposed to X-rays or cisplatin and treated with an ATR or Chk1 inhibitor, or by Fanconi anemia gene A knockout (FANCA ko). We assessed clonogenic survival, cell cycle regulation, micronuclei, free cytosolic double-stranded DNA, and the protein expression and activity of the cGAS/STING/IFN-1 pathway and related players. Cell survival, regulation of G2/M arrest, and formation of rupture-prone cGAS-positive micronuclei after genotoxic treatments were most affected by ATR inhibition and FANCA ko. In UM-SCC-1 cells only, 8 Gy X-rays promoted IFN-1 expression unaltered by abrogation of the DDR or concomitant increased TREX1 expression. At a higher dose of 20 Gy, this effect was observed only for concurrent Chk1- or ATR-inhibition. FANCA ko or cisplatin treatment was ineffective in this regard. Our observations open new perspectives for the enhancement of cGAS/STING/IFN-1-mediated antitumor immune response in HNSCC by hypofractionated or stereotactic radiotherapy concepts in multimodal settings with immuno-oncological strategies. |
DDC: | 570 Biowissenschaften 570 Life sciences 610 Medizin 610 Medical sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 04 Medizin |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-9604 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
Document type specification: | Scientific article |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | International journal of molecular sciences 24 19 |
Pages or article number: | 14900 |
Publisher: | Molecular Diversity Preservation International |
Publisher place: | Basel |
Issue date: | 2023 |
ISSN: | 1422-0067 |
Publisher DOI: | 10.3390/ijms241914900 |
Appears in collections: | DFG-491381577-G |
Files in This Item:
File | Description | Size | Format | ||
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the_cgasstingifn1_response_in-20231012103021973.pdf | 2.26 MB | Adobe PDF | View/Open |