Coussement Mina, Fazio Roberta, Audisio Alessandro, El Khoury Reem, Abbassi Fatima-Zahra, Assaf Irene, Conti Chiara, Gallio Chiara, Benhima Nada, Bregni Giacomo, Gkolfakis Paraskevas, Spagnolo Valentina, Anthoine Geraldine, Liberale Gabriel, Moretti Luigi, Martinive Philippe, Hendlisz Alain, Demetter Pieter, Sclafani Francesco
Institut Jules Bordet, Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), 1070 Brussels, Belgium.
Cerba Path, Division CMP, 1070 Brussels, Belgium.
Cancers (Basel). 2024 Jul 21;16(14):2606. doi: 10.3390/cancers16142606.
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 ( ≤ 0.04). In paired specimens, PD-L1-ICS reduction was especially observed following neoadjuvant long-course (chemo)radiotherapy ( = 0.03). PD-L1-ICS of ≥5% in surgical samples (HR: 0.17; = 0.02), and a biopsy-to-surgery increase in PD-L1-ICS (HR: 0.19; = 0.04) was predictive for longer disease-free survival, while the PD-L1-ICS of either ≥1% (HR 0.28; = 0.04) or ≥5% (HR 0.19; = 0.03) in surgical samples and the biopsy-to-surgery increase in PD-L1-ICS (HR: 0.20; = 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.
免疫检查点抑制剂和免疫相关生物标志物在直肠癌(RC)中的研究越来越多。我们回顾性分析了2000年至2020年在我们中心接受治疗的RC患者诊断性活检和切除样本中的PD-L1表达。根据肿瘤比例(TPS)、免疫细胞(ICS)和联合阳性评分(CPS)对PD-L1免疫染色(22C3克隆)进行评估。纳入了83例患者。在诊断时,基于TPS、ICS和CPS,分别有15.4%/0%、80.7%/37.4%和69.2%/25.6%的患者观察到PD-L1表达≥1%/≥5%。在手术时,相应的数据分别为4.6%/1.5%、60.2%/32.5%和50.7%/26.2%。使用1%的临界值且不考虑评分系统,手术样本中PD-L1的表达低于活检样本(≤0.04)。在配对样本中,新辅助长程(化疗)放疗后尤其观察到PD-L1-ICS降低(=0.03)。手术样本中PD-L1-ICS≥5%(HR:0.17;=0.02)以及活检到手术时PD-L1-ICS增加(HR:0.19;=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;=0.04)或≥5%(HR 0.19;=0.03)以及活检到手术时PD-L1-ICS增加(HR:0.20;=0.04)与更好的总生存期相关。我们的研究表明,RC中PD-L1的表达很大程度上反映了免疫细胞浸润,其在手术样本中的存在/增加预示着更好的预后。