Induction of micronuclei in cervical cancer treated with radiotherapy

Daijiro Kobayashi, Takahiro Oike, Kazutoshi Murata, Daisuke Irie, Yuka Hirota, Hiro Sato, Atsushi Shibata, Tatsuya Ohno

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Micronuclei (MN) trigger antitumor immune responses via the cyclic GMP-AMP synthase-signaling effector stimulator of interferon genes (cGAS-STING) pathway. Radiotherapy induces MN in peripheral blood lymphocytes. However, data for solid tumors are lacking. Here, we analyzed MN post-radiotherapy in solid tumor samples. Tumor biopsy specimens were obtained from seven prospectively recruited patients with cervical cancer, before treatment and after receiving radiotherapy at a dose of 10 Gy (in five fractions). The samples were stained with 4′,6-diamidino-2-phenylindole dihydrochloride, and 200 nuclei per sample were randomly identified and assessed for the presence of MN or apoptosis, based on nuclear morphology. The median number of MN-harboring nuclei was significantly greater in samples from patients treated with radiotherapy than in pre-treatment samples (151 (range, 16–327) versus 28 (range, 0–61); p = 0.015). No significant differences in the number of apoptotic nuclei were observed between pre-treatment and 10 Gy samples (5 (range, 0–30) versus 12 (range, 2–30); p = 0.30). This is the first report to demonstrate MN induction by radiotherapy in solid tumors. The results provide clinical evidence of the activation of antitumor immune responses by radiotherapy.

Original languageEnglish
Article number110
Pages (from-to)1-8
Number of pages8
JournalJournal of Personalized Medicine
Volume10
Issue number3
DOIs
Publication statusPublished - 2020 Sept
Externally publishedYes

Keywords

  • Abscopal effect
  • CGAS
  • Immunotherapy
  • Micronuclei
  • Radiotherapy
  • STING
  • Uterine cervical cancer

ASJC Scopus subject areas

  • Medicine (miscellaneous)

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