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
Department of Radiation Oncology, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371-8511, Japan.
Department of Radiotherapy, Saitama Cancer Center, Ina, Saitama 362-0806, Japan.
Oncol Lett. 2021 Jun;21(6):446. doi: 10.3892/ol.2021.12707. Epub 2021 Apr 6.
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.
放射治疗可在癌症微环境中引发免疫反应，这可能会影响临床结果。本研究旨在分析子宫颈鳞状细胞癌患者临床样本放疗后CD8 T细胞浸润和程序性死亡配体1（PD-L1）表达的变化。此外，本研究还试图分析这些免疫反应与临床结果之间的关联。对75例接受根治性放化疗或放疗的患者进行了回顾性分析。使用放疗前（RT前）和10 Gy放疗后（10 Gy后）的活检标本，通过免疫组织化学法测定CD8 T细胞浸润和PD-L1表达。PD-L1阳性率从RT前的5%（4/75）显著增加到10 Gy后的52%（39/75）（P<0.01）。尽管10 Gy后PD-L1阳性率有所增加，但RT前和10 Gy后与总生存期（OS）、局部区域控制（LC）和无进展生存期（PFS）均无显著关联。另一方面，所有患者的CD8 T细胞浸润密度均显著降低（中位数，RT前为23.1%，10 Gy后为16.9%；P=0.038）；然而，单纯接受放疗的患者中这一指标有增加趋势（中位数，RT前为17.7%，10 Gy后为24.0%；P=0.400）。值得注意的是，RT前或10 Gy后CD8 T细胞浸润高的患者与OS、LC和PFS呈正相关。因此，本分析表明CD8 T细胞浸润可能是接受放疗的宫颈癌患者的预后生物标志物。此外，免疫检查点抑制剂可能对接受过放疗的患者有效，因为放疗上调了宫颈癌标本中的PD-L1表达。
