Saigusa Susumu, Toiyama Yuji, Tanaka Koji, Inoue Yasuhiro, Mori Koichiro, Ide Shozo, Imaoka Hiroki, Kawamura Mikio, Mohri Yasuhiko, Kusunoki Masato
Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
Int J Clin Oncol. 2016 Oct;21(5):946-952. doi: 10.1007/s10147-016-0962-4. Epub 2016 Feb 26.
Programmed cell death ligand 1 (PD-L1) regulates immune responses through interaction with its receptor. PD-L1 is not only a predictor of poor prognosis but also a new therapeutic target in several malignancies. Neoadjuvant chemoradiotherapy (CRT) is an effective tool for local control of rectal cancer, but the disease recurrence rate remains high. The aim of this study was to retrospectively evaluate the correlation between PD-L1 expression and clinicopathological variables in rectal cancer after neoadjuvant CRT.
A total of 90 rectal cancer patients who underwent neoadjuvant CRT were enrolled in this study. We evaluated PD-L1 expression using immunohistochemistry. Moreover, we investigated the correlation between PD-L1 expression and tumor-infiltrating T cells, and between CD8- and Foxp3-positive cells.
Patients with high PD-L1 expression more frequently had vascular invasion and tumor recurrence compared to patients with low PD-L1 expression (P = 0.0225 and P = 0.0051). High PD-L1 expression was significantly associated with poor recurrence-free and overall survival (P = 0.0027 and P = 0.0357). Multivariate analysis revealed lymph node metastasis and high PD-L1 expression as independent risk factors for tumor recurrence (P = 0.0102 and P = 0.0374). Numbers of infiltrating CD8-positive cells in patients with high PD-L1 expression were significantly lower than in patients with low PD-L1 expression (P = 0.0322).
Our data suggest that inhibition of PD-L1 may be a new immunotherapeutic strategy to reduce tumor recurrence and improve prognosis in patients with rectal cancer after neoadjuvant CRT.
程序性细胞死亡配体1（PD-L1）通过与其受体相互作用来调节免疫反应。PD-L1不仅是预后不良的预测指标，也是多种恶性肿瘤的新治疗靶点。新辅助放化疗（CRT）是局部控制直肠癌的有效手段，但疾病复发率仍然很高。本研究的目的是回顾性评估新辅助CRT后直肠癌中PD-L1表达与临床病理变量之间的相关性。
本研究共纳入90例行新辅助CRT的直肠癌患者。我们采用免疫组织化学方法评估PD-L1表达。此外，我们还研究了PD-L1表达与肿瘤浸润性T细胞以及CD8和Foxp3阳性细胞之间的相关性。
与低PD-L1表达的患者相比，高PD-L1表达的患者更常出现血管侵犯和肿瘤复发（P = 0.0225和P = 0.0051）。高PD-L1表达与无复发生存期和总生存期差显著相关（P = 0.0027和P = 0.0357）。多因素分析显示淋巴结转移和高PD-L1表达是肿瘤复发的独立危险因素（P = 0.0102和P = 0.0374）。高PD-L1表达患者的浸润性CD8阳性细胞数量显著低于低PD-L1表达患者（P = 0.0322）。
我们的数据表明，抑制PD-L1可能是一种新的免疫治疗策略，可降低新辅助CRT后直肠癌患者的肿瘤复发率并改善预后。
