High linear energy transfer carbon-ion irradiation upregulates PD-L1 expression more significantly than X-rays in human osteosarcoma U2OS cells

Tiara Bunga Mayang Permata, Hiro Sato, Wenchao Gu, Sangeeta Kakoti, Yuki Uchihara, Yukihiko Yoshimatsu, Itaru Sato, Reona Kato, Motohiro Yamauchi, Keiji Suzuki, Takahiro Oike, Yoshito Tsushima, Soehartati Gondhowiardjo, Tatsuya Ohno, Takaaki Yasuhara, Atsushi Shibata

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Programmed death ligand 1 (PD-L1) expression on the surface of cancer cells affects the efficacy of anti-PD-1/PD-L1 immune checkpoint therapy. However, the mechanism underlying PD-L1 expression in cancer cells is not fully understood, particularly after ionizing radiation (IR). Here, we examined the impact of high linear energy transfer (LET) carbon-ion irradiation on the expression of PD-L1 in human osteosarcoma U2OS cells. We found that the upregulation of PD-L1 expression after high LET carbon-ion irradiation was greater than that induced by X-rays at the same physical and relative biological effectiveness (RBE) dose, and that the upregulation of PD-L1 induced by high LET carbon-ion irradiation was predominantly dependent on ataxia telangiectasia and Rad3-related (ATR) kinase activity. Moreover, we showed that the downstream signaling, e.g. STAT1 phosphorylation and IRF1 expression, was upregulated to a greater extent after high LET carbon-ion irradiation than X-rays, and that IRF1 upregulation was also ATR dependent. Finally, to visualize PD-L1 molecules on the cell surface in 3D, we applied immunofluorescence-based super-resolution imaging. The three-dimensional structured illumination microscopy (3D-SIM) analyses revealed substantial increases in the number of presented PD-L1 molecules on the cell surface after high LET carbon-ion irradiation compared with X-ray irradiation.

Original languageEnglish
Pages (from-to)773-781
Number of pages9
JournalJournal of radiation research
Volume62
Issue number5
DOIs
Publication statusPublished - Sep 1 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

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