Analysis of radiotherapy‑induced alteration of CD8+ T cells and PD‑L1 expression in patients with uterine cervical squamous cell carcinoma

Mori,Yasumasa; Sato,Hiro; Kumazawa,Takuya; Permata,Tiara Bunga Mayang; Yoshimoto,Yuya; Murata,Kazutoshi; Noda,Shin-Ei; Kaminuma,Takuya; Ando,Ken; Oike,Takahiro; Okonogi,Noriyuki; Okada,Kohei; Kakoti,Sangeeta; Suzuki,Keiji; Ikota,Hayato; Yokoo,Hideaki; Nakano,Takashi; Ohno,Tatsuya; Shibata,Atsushi

doi:10.3892/ol.2021.12707

Analysis of radiotherapy‑induced alteration of CD8+ T cells and PD‑L1 expression in patients with uterine cervical squamous cell carcinoma

Authors:
- Yasumasa Mori
- Hiro Sato
- Takuya Kumazawa
- Tiara Bunga Mayang Permata
- Yuya Yoshimoto
- Kazutoshi Murata
- Shin-Ei Noda
- Takuya Kaminuma
- Ken Ando
- Takahiro Oike
- Noriyuki Okonogi
- Kohei Okada
- Sangeeta Kakoti
- Keiji Suzuki
- Hayato Ikota
- Hideaki Yokoo
- Takashi Nakano
- Tatsuya Ohno
- Atsushi Shibata
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Affiliations: Department of Radiation Oncology, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371‑8511, Japan, Department of Radiation Oncology, Faculty of Medicine Universitas Indonesia, Dr Cipto Mangunkusumo Hospital, Jakarta 10430, Indonesia, Department of Radiation Oncology, Fukushima Medical University, Fukushima 960‑1247, Japan, Department of Radiation Oncology, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Hidaka, Saitama 350‑1298, Japan, National Institute of Radiological Sciences, National Institute for Quantum and Radiological Science and Technology, Chiba 263‑8555, Japan, Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852‑8523, Japan, Clinical Department of Pathology, Gunma University Hospital, Maebashi, Gunma 371‑8511, Japan, Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Signal Transduction Program, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Gunma 371‑8511, Japan
Published online on: April 6, 2021 https://doi.org/10.3892/ol.2021.12707
Article Number: 446

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Abstract

Radiotherapy induces an immune response in the cancer microenvironment that may influence clinical outcome. The present study aimed to analyse the alteration of CD8⁺ T‑cell infiltration and programmed death‑ligand 1 (PD‑L1) expression following radiotherapy in clinical samples from patients with uterine cervical squamous cell carcinoma. Additionally, the current study sought to analyse the association between these immune responses and clinical outcomes. A total of 75 patients who received either definitive chemoradiotherapy or radiotherapy were retrospectively analyzed. CD8⁺ T‑cell infiltration and PD‑L1 expression were determined by immunohistochemistry using biopsy specimens before radiotherapy (pre‑RT) and after 10 Gy radiotherapy (post‑10 Gy). The PD‑L1⁺ rate was significantly increased from 5% (4/75) pre‑RT to 52% (39/75) post‑10 Gy (P<0.01). Despite this increase in the PD‑L1⁺ rate post‑10 Gy, there was no significant association between both pre‑RT and post‑10 Gy and overall survival (OS), locoregional control (LC) and progression‑free survival (PFS). On the other hand, the CD8⁺ T‑cell infiltration density was significantly decreased for all patients (median, 23.1% pre‑RT vs. 16.9% post‑10 Gy; P=0.038); however, this tended to increase in patients treated with radiotherapy alone (median, 17.7% pre‑RT vs. 24.0% post‑10 Gy; P=0.400). Notably, patients with high CD8⁺ T‑cell infiltration either pre‑RT or post‑10 Gy exhibited positive associations with OS, LC and PFS. Thus, the present analysis suggested that CD8⁺ T‑cell infiltration may be a prognostic biomarker for patients with cervical cancer receiving radiotherapy. Furthermore, immune checkpoint inhibitors may be effective in patients who have received radiotherapy, since radiotherapy upregulated PD‑L1 expression in cervical cancer specimens.

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