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

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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2 Citations (Scopus)

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 associa- tion between these immune responses and clinical outcomes. A total of 75 patients who received either definitive chemoradio- therapy or radiotherapy were retrospectively analyzed. CD8+ T-cell infiltration and PD-L1 expression were determined by immunohistochemistry using biopsy specimens before radio- therapy (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 upregu- lated PD-L1 expression in cervical cancer specimens.

Original languageEnglish
Article number446
JournalOncology Letters
Volume21
Issue number6
DOIs
Publication statusPublished - Jun 2021

Keywords

  • CD8 T cell
  • Cervical cancer
  • Immune modulation
  • Programmed death-ligand 1
  • Radiotherapy
  • Tumor microenvironment

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