直肠癌放化疗前后程序性细胞死亡配体 1 表达和 CD8 阳性 T 细胞浸润的模式。
Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer.
机构信息
Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo 135-8550, Japan; Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo 135-8550, Japan.
出版信息
Eur J Cancer. 2018 Mar;91:11-20. doi: 10.1016/j.ejca.2017.12.005. Epub 2018 Jan 9.
BACKGROUND
The synergistic effect of combining immune checkpoint inhibitors with radiotherapy was reported recently, but there are few studies on programmed cell death-ligand 1 (PD-L1) expression in rectal cancer treated by preoperative chemoradiotherapy (CRT). The aim of the present study was to investigate the PD-L1 expression status before and after CRT and its association with clinicopathological characteristics and recurrence in rectal cancer.
METHODS
Immunostainings of PD-L1 and CD8 were performed in 287 patients with rectal cancer treated by CRT. PD-L1 expression on the tumour cells (tPD-L1) and on the stromal immune cells (iPD-L1) was evaluated before and after CRT. CD8+ cell density in tumour area (tCD8+) before CRT and in the stromal area (sCD8+) before and after CRT was also evaluated.
RESULTS
High tPD-L1 expression was observed in only three patients (1.0%). High iPD-L1 expression significantly increased from 31.7% before CRT to 49.2% after CRT (P < 0.0001). The increase in high iPD-L1 expression after CRT was only observed in patients with tumour regression grades 1 and 2. High iPD-L1 expression was associated with high tCD8+ cell density before CRT (P < 0.0001) and sCD8+ cell density after CRT (P < 0.0001). High tCD8+ cell density before CRT was associated with better disease-free survival (DFS) (P = 0.0331), but its improved effect on DFS could be observed in patients with high iPD-L1 expression (P = 0.0081), not in patients with low iPD-L1 expression (P = 0.516).
CONCLUSION
The present study demonstrated the significant correlations between iPD-L1 expression and CD8+ cell density both before and after CRT.
背景
最近有报道称免疫检查点抑制剂与放疗联合具有协同作用，但关于术前放化疗（CRT）治疗的直肠癌中程序性死亡配体 1（PD-L1）表达的研究较少。本研究旨在探讨 CRT 前后 PD-L1 的表达状态及其与直肠癌临床病理特征和复发的关系。
方法
对 287 例接受 CRT 的直肠癌患者进行 PD-L1 和 CD8 的免疫组化染色。评估 CRT 前后肿瘤细胞（tPD-L1）和间质免疫细胞（iPD-L1）上的 PD-L1 表达。CRT 前肿瘤区域（tCD8+）和 CRT 前后间质区域（sCD8+）的 CD8+细胞密度也进行了评估。
结果
仅 3 例（1.0%）患者观察到高 tPD-L1 表达。高 iPD-L1 表达显著从 CRT 前的 31.7%增加到 CRT 后的 49.2%（P<0.0001）。仅在肿瘤消退分级 1 和 2 的患者中观察到 CRT 后高 iPD-L1 表达的增加。高 iPD-L1 表达与 CRT 前高 tCD8+细胞密度（P<0.0001）和 CRT 后 sCD8+细胞密度（P<0.0001）相关。CRT 前高 tCD8+细胞密度与无病生存（DFS）相关（P=0.0331），但在高 iPD-L1 表达的患者中观察到其对 DFS 的改善作用（P=0.0081），而在低 iPD-L1 表达的患者中则无（P=0.516）。
结论
本研究表明 CRT 前后 iPD-L1 表达与 CD8+细胞密度之间存在显著相关性。
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