Radiation-induced alterations in immunogenicity of a murine pancreatic ductal adenocarcinoma cell line

Sci Rep. 2020 Jan 20;10(1):686. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / metabolism*
  • Animals
  • B7-H1 Antigen / metabolism*
  • Carcinoma, Pancreatic Ductal / immunology*
  • Carcinoma, Pancreatic Ductal / radiotherapy
  • Cell Cycle / radiation effects
  • Cell Line, Tumor
  • Cell Proliferation / radiation effects
  • Cell Survival / radiation effects
  • Clone Cells / cytology
  • Clone Cells / metabolism
  • Clone Cells / radiation effects
  • Dose-Response Relationship, Radiation
  • Mice
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / radiotherapy
  • Radiation Tolerance
  • Time Factors

Substances

  • B7-H1 Antigen
  • Cd274 protein, mouse
  • 5'-Nucleotidase