Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany.
Department of Nephropathology, Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany.
Eur J Cancer. 2016 Sep;65:52-60. doi: 10.1016/j.ejca.2016.06.015. Epub 2016 Jul 25.
The influence of neoadjuvant radiochemotherapy (RCT) on programmed death-ligand 1 (PD-L1) expression, a predictive marker for programmed cell death protein 1 (PD-1) inhibitor therapy, was studied on tumour and inflammatory cells in rectal adenocarcinoma patients along with its prognostic value.
PD-L1 immunohistochemistry was performed on tissue microarrays of 103 pre-RCT biopsies and 159 post-RCT surgical specimens (central tumour, invasive front and normal tissue) of 199 patients. In 63 patients, both samples were available. Proportion and maximum intensity of PD-L1-positive (PD-L1+) cells were evaluated.
RCT increased the proportion of PD-L1-expressing cancer cells from 2.1% to 7.8% in the central tumour (p < 0.001) or 9.3% in the invasive front (p < 0.001). Cancer cell PD-L1 on its own could not predict prognosis. High PD-L1 expression on pre-RCT inflammatory cells (maximum intensity: p = 0.048) and post-RCT invasive front inflammatory cells (p = 0.010) correlated with improved no evidence of disease survival. In multivariate analysis, the combination of low PD-L1 in cancer and inflammatory cells was an independent negative prognostic marker for overall survival (OS) pre-RCT (Cox's proportional hazard ratio 0.438, p = 0.045) and in the invasive front post-RCT (Cox's proportional hazard ratio 0.257, p = 0.030).
Neoadjuvant RCT is associated with an increased PD-L1 expression in rectal adenocarcinoma patients, which should prompt clinical trials combining radiotherapy and PD-1/PD-L1 pathway blockade. Combined low PD-L1 expression on tumour and inflammatory cells is an independent negative prognostic marker for OS in RCT of rectal adenocarcinoma.
新辅助放化疗（RCT）对预测性标志物程序性死亡配体 1（PD-L1）表达的影响，以及对直肠腺癌患者肿瘤和炎症细胞的影响及其预后价值进行了研究。
对 199 例患者的 103 例 RCT 前活检和 159 例 RCT 后手术标本（中央肿瘤、浸润前缘和正常组织）的组织微阵列进行 PD-L1 免疫组织化学染色。在 63 例患者中，两种样本均可用。评估 PD-L1+细胞的比例和最大强度。
RCT 使中央肿瘤（p<0.001）或浸润前缘（p<0.001）中 PD-L1 表达的癌细胞比例从 2.1%增加到 7.8%或 9.3%。单独的癌细胞 PD-L1 不能预测预后。RCT 前炎症细胞（最大强度：p=0.048）和 RCT 后浸润前缘炎症细胞的高 PD-L1 表达与无疾病生存改善相关。多变量分析显示，癌症和炎症细胞中低 PD-L1 的组合是 RCT 前总体生存（OS）的独立负预后标志物（Cox 比例风险比 0.438，p=0.045）和 RCT 后浸润前缘的独立负预后标志物（Cox 比例风险比 0.257，p=0.030）。
新辅助 RCT 与直肠腺癌患者 PD-L1 表达增加相关，这应促使临床研究联合放疗和 PD-1/PD-L1 通路阻断。RCT 中肿瘤和炎症细胞中 PD-L1 表达水平低的联合是 OS 的独立负预后标志物。
