Immune checkpoint inhibitors and immune-related biomarkers are increasingly investigated in rectal cancer (RC). We retrospectively analysed PD-L1 expression in diagnostic biopsy and resection samples from RC patients treated at our centre between 2000 and 2020. PD-L1 immunostaining (22C3 clone) was evaluated according to tumour proportion (TPS), immune cell (ICS), and the combined positive score (CPS). Eighty-three patients were included. At diagnosis, PD-L1 expression ≥1%/≥5% was observed in 15.4%/0%, 80.7%/37.4%, and 69.2%/25.6% of patients based on TPS, ICS, and CPS, respectively. At surgery, the respective figures were 4.6%/1.5%, 60.2%/32.5%, and 50.7%/26.2%. Using the 1% cut-off and regardless of the scoring system, PD-L1 was less expressed in surgery than biopsy samples (p≤ 0.04). In paired specimens, PD-L1-ICS reduction was especially observed following neoadjuvant long-course (chemo)radiotherapy (p= 0.03). PD-L1-ICS of ≥5% in surgical samples (HR: 0.17;p= 0.02), and a biopsy-to-surgery increase in PD-L1-ICS (HR: 0.19;p= 0.04) was predictive for longer disease-free survival, while the PD-L1-ICS of either ≥1% (HR 0.28;p= 0.04) or ≥5% (HR 0.19;p= 0.03) in surgical samples and the biopsy-to-surgery increase in PD-L1-ICS (HR: 0.20;p= 0.04) were associated with better overall survival. Our study suggests that PD-L1 expression in RC is largely reflective of immune cell infiltration, and its presence/increase in surgical samples predicts better outcomes.
免疫检查点抑制剂及相关生物标志物在直肠癌领域的研究日益深入。本研究回顾性分析了2000年至2020年间在本中心接受治疗的直肠癌患者诊断活检样本与手术切除样本中的PD-L1表达情况。采用22C3克隆抗体进行免疫组化染色,分别依据肿瘤细胞阳性比例评分(TPS)、免疫细胞评分(ICS)及综合阳性评分(CPS)进行评估。共纳入83例患者。诊断时,基于TPS、ICS和CPS评分标准,分别有15.4%/0%、80.7%/37.4%和69.2%/25.6%的患者PD-L1表达≥1%/≥5%。手术时,相应比例分别为4.6%/1.5%、60.2%/32.5%和50.7%/26.2%。采用1%为阈值时,无论使用何种评分系统,手术样本的PD-L1表达均低于活检样本(p≤0.04)。在配对样本分析中,新辅助长程放(化)疗后尤其观察到PD-L1-ICS评分下降(p=0.03)。手术样本中PD-L1-ICS≥5%(HR:0.17;p=0.02)以及活检至手术期间PD-L1-ICS评分升高(HR:0.19;p=0.04)可预测更长的无病生存期;而手术样本中PD-L1-ICS≥1%(HR:0.28;p=0.04)或≥5%(HR:0.19;p=0.03),以及活检至手术期间PD-L1-ICS评分升高(HR:0.20;p=0.04)均与更好的总生存期相关。本研究表明,直肠癌中PD-L1表达主要反映免疫细胞浸润程度,手术样本中PD-L1的存在/升高预示着更好的临床结局。