Open Access

Expression of non‑homologous end joining factor, Ku80, is negatively correlated with PD‑L1 expression in cancer cells after X‑ray irradiation

  • Authors:
    • Takuya Kumazawa
    • Yasumasa Mori
    • Hiro Sato
    • Tiara Bunga Mayang Permata
    • Yuki Uchihara
    • Shin-Ei Noda
    • Kohei Okada
    • Sangeeta Kakoti
    • Keiji Suzuki
    • Hayato Ikota
    • Hideaki Yokoo
    • Soehartati Gondhowiardjo
    • Takashi Nakano
    • Tatsuya Ohno
    • Atsushi Shibata
  • View Affiliations

  • Published online on: November 23, 2021     https://doi.org/10.3892/ol.2021.13147
  • Article Number: 29
  • Copyright: © Kumazawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The growing importance of antitumour immunity by cancer immunotherapy has prompted studies on radiotherapy‑induced immune response. Previous studies have indicated that programmed cell death‑1 ligand (PD‑L1) expression is regulated by DNA damage signalling. However, PD‑L1 up‑regulation after radiotherapy has not been fully investigated at the clinical level, particularly in the context of expression of DNA repair factors. The present study examined the correlation of mRNA expression between PD‑L1 and non‑homologous end joining (NHEJ) factors using The Cancer Genome Atlas database analysis. Among NHEJ factors, Ku80 mRNA expression was negatively correlated with PD‑L1 mRNA expression levels in several types of cancer (colon adenocarcinoma, breast invasive carcinoma, skin cutaneous melanoma, lung adenocarcinoma, head and neck squamous cell carcinoma, uterine corpus endometrial carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma). To verify the negative correlation in clinical samples, the present study analysed whether Ku80 expression levels affected PD‑L1 up‑regulation after radiotherapy using cervical squamous cell carcinoma samples. Quantitative evaluation using software analysis of immunohistochemically stained slides revealed that patients with low Ku80 positivity in biopsy specimens demonstrated increased PD‑L1 expression levels after 10 Gy irradiation (Spearman's rank correlation coefficient=‑0.274; P=0.017). Furthermore, PD‑L1 induction levels in tumour cells after 10 Gy of irradiation were significantly inversely correlated with Ku80 expression levels (Spearman's rank correlation coefficient=‑0.379; P<0.001). The present study also confirmed that short interfering RNA‑mediated Ku80 depletion was associated with greater X‑ray‑induced PD‑L1 up‑regulation in HeLa cells. These results indicated that radiotherapy could enhance PD‑L1 induction in tumour cells with low Ku80 expression in a clinical setting. Furthermore, these data highlighted Ku80 as a potential predictive biomarker for immune checkpoint therapy combined with radiotherapy.
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January-2022
Volume 23 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Kumazawa T, Mori Y, Sato H, Permata TB, Uchihara Y, Noda S, Okada K, Kakoti S, Suzuki K, Ikota H, Ikota H, et al: Expression of non‑homologous end joining factor, Ku80, is negatively correlated with PD‑L1 expression in cancer cells after X‑ray irradiation. Oncol Lett 23: 29, 2022
APA
Kumazawa, T., Mori, Y., Sato, H., Permata, T.B., Uchihara, Y., Noda, S. ... Shibata, A. (2022). Expression of non‑homologous end joining factor, Ku80, is negatively correlated with PD‑L1 expression in cancer cells after X‑ray irradiation. Oncology Letters, 23, 29. https://doi.org/10.3892/ol.2021.13147
MLA
Kumazawa, T., Mori, Y., Sato, H., Permata, T. B., Uchihara, Y., Noda, S., Okada, K., Kakoti, S., Suzuki, K., Ikota, H., Yokoo, H., Gondhowiardjo, S., Nakano, T., Ohno, T., Shibata, A."Expression of non‑homologous end joining factor, Ku80, is negatively correlated with PD‑L1 expression in cancer cells after X‑ray irradiation". Oncology Letters 23.1 (2022): 29.
Chicago
Kumazawa, T., Mori, Y., Sato, H., Permata, T. B., Uchihara, Y., Noda, S., Okada, K., Kakoti, S., Suzuki, K., Ikota, H., Yokoo, H., Gondhowiardjo, S., Nakano, T., Ohno, T., Shibata, A."Expression of non‑homologous end joining factor, Ku80, is negatively correlated with PD‑L1 expression in cancer cells after X‑ray irradiation". Oncology Letters 23, no. 1 (2022): 29. https://doi.org/10.3892/ol.2021.13147