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Publikasi Scopus 926 artikel (Per 14 Maret 2022)
Publikasi Scopus 926 artikel (Per 14 Maret 2022)
High linear energy transfer carbon-ion irradiation upregulates PD-L1 expression more significantly than X-rays in human osteosarcoma U2OS cells
2021
Journal of Radiation Research
62
5
773
781
2
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85115918333&doi=10.1093%2fjrr%2frrab050&partnerID=40&md5=a1550b83230aa8ab90277d2716e9a556
Department of Radiation Oncology, Gunma University, Gunma, Maebashi, 371-8511, Japan; Department of Radiation Oncology, Faculty of Medicine Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital, Jakarta, 10430, Indonesia; Gunma University Heavy IonMedical Center, Gunma, Maebashi, 371-8511, Japan; Gunma University Initiative for Advanced Research (GIAR), Gunma University, Gunma, Maebashi, 371-8511, Japan; Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School OfMedicine, Gunma, Maebashi, 371-8511, Japan; Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School OfMedicine, The University OfTokyo, Bunkyo-ku, Tokyo, 113-8655, Japan; Department of Radiation Biology and Protection, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, 852-8523, Japan; Department of Radiation Medical Science, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, 852-8523, Japan
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. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.
Carbon; Cell membranes; Cytology; Diseases; Ionizing radiation; Ions; Molecules; Oncology; Radiotherapy; Anti-PD-1/programmed death ligand 1 therapy; Carbon ion therapy; Carbon ions; DNA damage response; High linear energy transfer carbon-ion therapy; High linear energy transfers; Human osteosarcoma; Ions irradiation; Programmed death ligand 1 expression; Up-regulation; Energy transfer; 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one; 3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide; ATM protein; ATM protein, human; ATR protein, human; CD274 protein, human; interferon regulatory factor 1; IRF1 protein, human; messenger RNA; morpholine derivative; programmed death 1 ligand 1; pyrazine derivative; pyrone derivative; RNA; STAT1 protein; STAT1 protein, human; sulfone; tumor p
Oxford University Press
04493060
34196706
Article
Q2
643
7838