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Induction of Micronuclei in Cervical Cancer Treated with Radiotherapy
Daijiro Kobayashi1, Takahiro Oike2, Kazutoshi Murata3
1Department of Radiation Oncology, Gunma Prefectural Cancer Center, Gunma 373-8550, Japan.
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.
Insights
Radiotherapy increases micronuclei (MN) in solid tumors, activating antitumor immune responses via the cGAS-STING pathway. This study provides the first clinical evidence of MN induction in solid tumors post-radiotherapy.
Area of Science:
- Oncology
- Immunology
- Radiotherapy
Background:
- Micronuclei (MN) are known to activate antitumor immune responses through the cyclic GMP-AMP synthase-signaling effector stimulator of interferon genes (cGAS-STING) pathway.
- Radiotherapy has been shown to induce MN in lymphocytes, but its effect on solid tumors was previously uninvestigated.
Purpose of the Study:
- To investigate the induction of micronuclei (MN) in solid tumors following radiotherapy.
- To provide clinical evidence for radiotherapy-induced antitumor immune responses in solid tumors.
Main Methods:
- Tumor biopsy specimens were collected from cervical cancer patients before and after 10 Gy radiotherapy.
- Nuclei were stained and assessed for MN and apoptosis using 4',6-diamidino-2-phenylindole dihydrochloride staining.
- Quantification of MN-harboring and apoptotic nuclei was performed on 200 nuclei per sample.
Main Results:
- A significant increase in MN-harboring nuclei was observed in post-radiotherapy samples compared to pre-treatment samples (median 151 vs. 28, p=0.015).
- No significant difference in the number of apoptotic nuclei was found between pre-treatment and post-radiotherapy samples (median 5 vs. 12, p=0.30).
Conclusions:
- Radiotherapy significantly induces micronuclei (MN) formation in solid tumors.
- This study presents the first clinical evidence that radiotherapy activates antitumor immune responses in solid tumors through MN induction.
