Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer
Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer
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DOI：
10.1016/j.ejca.2017.12.005
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发表时间：
2018-03-01
影响因子：
8.4
通讯作者：
Ueno, Masashi
中科院分区：
文献类型：
--
作者：
Ogura, Atsushi;Akiyoshi, Takashi;Ueno, Masashi
背景：免疫检查点抑制剂联合放疗的增效作用最近有报道，但对术前放化疗（CRT）治疗直肠癌中程序性细胞死亡配体1 （PD-L1）表达的研究较少。本研究的目的是探讨CRT前后PD-L1的表达状况及其与直肠癌临床病理特征和复发的关系。方法：对287例经CRT治疗的直肠癌患者进行PD-L1和CD8免疫染色。检测CRT前后肿瘤细胞（tPD-L1）和基质免疫细胞（iPD-L1）上PD-L1的表达。同时评价CRT前肿瘤区CD8+细胞密度（tCD8+）及CRT前后间质区CD8+细胞密度（sCD8+）。结果：tPD-L1高表达仅3例（1.0%）。高iPD-L1表达由CRT前的31.7%显著升高至CRT后的49.2% （P < 0.0001）。仅在肿瘤消退1级和2级患者中观察到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后高sCD8+细胞密度（P < 0.0001）相关。CRT前高tCD8+细胞密度与较好的无病生存（DFS）相关（P = 0.0331），但在iPD-L1高表达患者中可观察到其改善DFS的作用（P = 0.0081），而在iPD-L1低表达患者中则无改善作用（P = 0.516）。结论：本研究显示CRT前后iPD-L1表达与CD8+细胞密度有显著相关性。(C) 2017 Elsevier Ltd.版权所有。
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. (C) 2017 Elsevier Ltd. All rights reserved.