Journal Article

DKFZ-2020-00253

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Radiation-induced alterations in immunogenicity of a murine pancreatic ductal adenocarcinoma cell line.

Schröter, P. (First author)DKFZ* ; Hartmann, L.DKFZ* ; Osen, W.DKFZ* ; Baumann, D.DKFZ* ; Offringa, R.DKFZ* ; Eisel, D.DKFZ* ; Debus, J.Extern* ; Eichmüller, S. B. (Last author)DKFZ* ; Rieken, S. (Last author)DKFZ*

2020
Macmillan Publishers Limited, part of Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41598-020-57456-2

Abstract: Pancreatic ductal adenocarcinoma (PDA) is highlighted by resistance to radiotherapy with the possible exception of hypofractionated irradiation. As single photon doses were reported to increase immunogenicity, we investigated dose-dependent irradiation effects on clonogenic survival, expression of immunologically relevant cell surface molecules and susceptibility to cytotoxic T cell (CTL) mediated killing using a murine PDA cell line. Clonogenicity decreased in a dose-responsive manner showing enhanced radioresistance at single photon doses below 5 Gy. Cell cycle analysis revealed a predominant G2/M arrest, being most pronounced 12 h after irradiation. Polyploidy increased in a dose- and time-dependent manner reaching a maximum frequency 60 h following irradiation with 10 Gy. Irradiation increased surface expression of MHC class I molecules and of immunological checkpoint molecules PDL-1 and CD73, especially at doses ≥ 5 Gy, but not of MHC class II molecules and CXCR4 receptors. Cytotoxicity assays revealed increased CTL lysis of PDA cells at doses ≥ 5 Gy. For the PDA cell line investigated, our data show for the first time that single photon doses ≥ 5 Gy effectively inhibit colony formation and induce a G2/M cell cycle arrest. Furthermore, expression levels of immunomodulatory cell surface molecules became altered possibly enhancing the susceptibility of tumour cells to CTL lysis.

Note: #EA:D210#LA:D210#E050#

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Contributing Institute(s):

1. Arbeitsgruppe GMP & T-Zelltherapie (D210)
2. Molekulare Grundlagen Gastrointestinaler Tumoren (D200)
3. E050 KKE Strahlentherapie (E050)

Research Program(s):

1. 314 - Tumor immunology (POF3-314) (POF3-314)

Appears in the scientific report 2020

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