Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China.
Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangzhou, China.
Int J Radiat Oncol Biol Phys. 2020 Sep 1;108(1):286-294. doi: 10.1016/j.ijrobp.2020.01.020. Epub 2020 Jan 28.
Despite good preclinical evidence, clinical data on the effect of neoadjuvant chemoradiation therapy (CRT) on expression of immune markers in esophageal cancer are limited. This study aimed to evaluate the changes in indoleamine 2,3-dioxygenase 1 (IDO1) expression, programmed cell death-ligand 1 (PD-L1) expression, and CD8+ tumor-infiltrating lymphocyte status after neoadjuvant CRT and the prognostic significance in esophageal squamous cell carcinoma (ESCC).
Between 2003 and 2017, 138 patients with ESCC who underwent neoadjuvant CRT and esophagectomy without achieving pathologic complete response were included for analysis. Both pre-CRT biopsies and post-CRT surgical specimens were available in 82 patients. Immunohistochemistry of IDO1, PD-L1, and CD8 density were analyzed.
Among 82 paired samples, the expression levels of IDO1 and PD-L1 and CD8 density increased significantly after neoadjuvant CRT (P < .01 for all). Patients with high IDO1 expression after CRT had poorer overall survival (P = .001) and recurrence-free survival (P < .001) than those with low IDO1 expression. High post-CRT CD8 density was significantly correlated with more favorable overall survival (P = .01) and recurrence-free survival (P = .008). Neither pre- nor post-CRT PD-L1 expression was an independent prognostic factor for survival. Stratification analysis revealed that patients with combined low IDO1 expression and high CD8 density after CRT were significantly associated with better survival than other subgroups. The major findings were reproducible in an independent validation cohort.
IDO1 and PD-L1 expression and CD8 density increased significantly after neoadjuvant CRT in ESCC. The post-CRT IDO1 expression and CD8 density could serve as prognostic biomarkers for survival.
尽管有很好的临床前证据，但关于新辅助放化疗（CRT）对食管癌免疫标志物表达影响的临床数据有限。本研究旨在评估新辅助 CRT 后吲哚胺 2,3-双加氧酶 1（IDO1）表达、程序性死亡配体 1（PD-L1）表达和 CD8+肿瘤浸润淋巴细胞状态的变化，并探讨其在食管鳞状细胞癌（ESCC）中的预后意义。
2003 年至 2017 年间，138 例接受新辅助 CRT 联合手术治疗但未达到病理完全缓解的 ESCC 患者纳入本研究进行分析。82 例患者的新辅助 CRT 前活检和 CRT 后手术标本均可用。分析 IDO1、PD-L1 和 CD8 密度的免疫组织化学。
在 82 对配对样本中，新辅助 CRT 后 IDO1 和 PD-L1 的表达水平以及 CD8 密度显著升高（均 P <.01）。CRT 后 IDO1 高表达患者的总生存（P =.001）和无复发生存（P <.001）均较差，而 IDO1 低表达患者的总生存和无复发生存均较好。高 CRT 后 CD8 密度与更有利的总生存（P =.01）和无复发生存（P =.008）显著相关。无论是 CRT 前还是 CRT 后 PD-L1 表达均不是生存的独立预后因素。分层分析显示，CRT 后 IDO1 表达和 CD8 密度均低的患者的生存显著优于其他亚组。在独立验证队列中也得到了类似的主要发现。
ESCC 患者新辅助 CRT 后 IDO1 和 PD-L1 表达以及 CD8 密度显著增加。CRT 后 IDO1 表达和 CD8 密度可作为生存的预后生物标志物。
