Graduate Institute of Biomedical Science, China Medical University, Taichung, 40402, Taiwan.
Department of Pathology, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan.
J Cancer Res Clin Oncol. 2019 Apr;145(4):1043-1053. doi: 10.1007/s00432-019-02874-7. Epub 2019 Mar 14.
PURPOSE/BACKGROUND: Radiotherapy has been recently reported to boost the therapeutic response of immune checkpoint blockade (ICB); however, few studies have focused on programmed cell death-ligand 1 (PD-L1) expression in locally advanced rectal cancer (LARC) patients who receive preoperative neoadjuvant chemoradiotherapy (neoCRT). The aim of the present study was to investigate the PD-L1 expression status and CD8+ intra-tumoral infiltrating lymphocytes (TILs) before and after neoCRT and its association with clinicopathological characteristics in rectal cancer.
Immunostainings of PD-L1 and CD8+ TILs were performed in 112 pair-matched LARC patients treated by neoCRT. Tumor PD-L1 expression and CD8+ TILs within the tumor microenvironment before and after neoCRT were evaluated via immunohistochemistry.
High tumor PD-L1 expression was significantly increased from 50 to 63%, and high CD8+ TILs counts were also slightly increased from 32 to 35% after neoCRT treatment. High tumor PD-L1 before and after neoCRT was associated with improved disease-free survival (DFS, pre-neoCRT: p = 0.003 and post-neoCRT: p = 0.003) and overall survival (OS, pre-neoCRT: p = 0.045 and post-neoCRT: p = 0.0001). High CD8+ TILs before neoCRT was associated with improved DFS (p = 0.057), and it was significantly associated with improved DFS after neoCRT (p = 0.039). Patients with high tumor PD-L1 and CD8+ TILs before and after neoCRT were significantly associated with improved DFS (pre-neoCRT: p = 0.004 and post-neoCRT: p = 0.006).
The present results provide evidence that tumor PD-L1 expression and recruitment of CD8+ TILs within the tumor microenvironment were increased by neoCRT treatment. Tumor PD-L1 and CD8+ TILs are prognostic biomarkers for the survival of LARC patients treated with neoCRT.
目的/背景：放疗最近被报道可以增强免疫检查点阻断（ICB）的治疗反应；然而，很少有研究关注接受术前新辅助放化疗（neoCRT）的局部晚期直肠癌（LARC）患者中程序性死亡配体 1（PD-L1）的表达。本研究旨在探讨 neoCRT 前后 PD-L1 表达状态和 CD8+肿瘤内浸润淋巴细胞（TILs）及其与直肠癌临床病理特征的关系。
对 112 例接受 neoCRT 治疗的 LARC 患者进行 PD-L1 和 CD8+TIL 的免疫组化染色。通过免疫组化评估 neoCRT 前后肿瘤 PD-L1 表达和肿瘤微环境中的 CD8+TILs。
高肿瘤 PD-L1 表达从 50%显著增加到 63%，高 CD8+TILs 计数也从 32%略微增加到 35%。 neoCRT 前后高肿瘤 PD-L1 与无病生存（DFS，neoCRT 前：p=0.003 和 neoCRT 后：p=0.003）和总生存（OS，neoCRT 前：p=0.045 和 neoCRT 后：p=0.0001）改善相关。 neoCRT 前高 CD8+TILs 与 DFS 改善相关（p=0.057），与 neoCRT 后 DFS 显著相关（p=0.039）。 neoCRT 前后高肿瘤 PD-L1 和 CD8+TILs 的患者与 DFS 改善显著相关（neoCRT 前：p=0.004 和 neoCRT 后：p=0.006）。
本研究结果提供了证据表明 neoCRT 治疗增加了肿瘤 PD-L1 表达和肿瘤微环境中 CD8+TILs 的募集。肿瘤 PD-L1 和 CD8+TILs 是 neoCRT 治疗 LARC 患者生存的预后生物标志物。
