Background/Objectives: Immune checkpoint inhibitors (ICIs) benefit some lung cancer patients, but their efficacy is limited in advanced lung adenocarcinoma (LUAD) withEGFRmutations (EGFRm), largely due to a non-immunogenic tumour microenvironment (TME). Furthermore,EGFRmLUAD patients often experience increased toxicity with ICIs. CD73, an ectonucleotidase involved in adenosine production, promotes tumour immune evasion and could represent a novel therapeutic target. This study investigates CD73 expression in LUAD withEGFRalterations and its clinico-pathological correlations. Methods: CD73 expression in tumour (CD73TC) and stromal (CD73SC) cells was assessed in 76 treatment-naive LUAD patients using immunohistochemistry (IHC) (D7F9A clone) alongside IHC PD-L1 (22C3 clone).EGFRalterations were identified by molecular sequencing and FISH. Event-free survival (EFS) was analysed based on CD73TCexpression. Results: CD73TCexpression was observed in 66% of cases, with high expression (Tumour Proportion Score > 50%) correlating with improved EFS (p= 0.045). CD73TCand PD-L1 expression were not significantly correlated (p= 0.44), although a weak inverse trend was observed. CD73SCexpression was detected in 18% of cases, predominantly in early-stage (p= 0.037), PD-L1-negative (p= 0.030), and non-EGFR-amplified (p= 0.0018) tumours. No significant associations were found with disease stage, histological subtype,EGFRmutation type, and amplification. Conclusions: CD73 expression inEGFRmLUAD is heterogeneous and associated with diverse TME profiles. These findings support the potential of CD73 as a predictive biomarker and therapeutic target, highlighting its clinical relevance inEGFRmLUAD.
**背景/目的：** 免疫检查点抑制剂（ICIs）使部分肺癌患者获益，但其在携带EGFR突变（EGFRm）的晚期肺腺癌（LUAD）中的疗效有限，这主要归因于非免疫原性的肿瘤微环境（TME）。此外，EGFRm LUAD患者使用ICIs时常出现毒性增加。CD73是一种参与腺苷产生的外核苷酸酶，可促进肿瘤免疫逃逸，可能代表一个新的治疗靶点。本研究探讨了CD73在伴有EGFR改变的LUAD中的表达及其临床病理学相关性。 **方法：** 采用免疫组织化学（IHC）方法（D7F9A克隆抗体），结合PD-L1 IHC检测（22C3克隆抗体），评估了76例初治LUAD患者肿瘤细胞（CD73TC）和间质细胞（CD73SC）的CD73表达。通过分子测序和FISH技术鉴定EGFR改变。根据CD73TC表达情况分析无事件生存期（EFS）。 **结果：** 66%的病例观察到CD73TC表达，其中高表达（肿瘤比例评分 > 50%）与改善的EFS相关（p = 0.045）。CD73TC与PD-L1表达无显著相关性（p = 0.44），但观察到微弱的负相关趋势。18%的病例检测到CD73SC表达，主要见于早期（p = 0.037）、PD-L1阴性（p = 0.030）以及非EGFR扩增（p = 0.0018）的肿瘤。未发现CD73表达与疾病分期、组织学亚型、EGFR突变类型及扩增状态存在显著关联。 **结论：** CD73在EGFRm LUAD中的表达具有异质性，并与不同的TME特征相关。这些发现支持CD73作为预测性生物标志物和治疗靶点的潜力，突显了其在EGFRm LUAD中的临床相关性。
Exploring the Expression of CD73 in Lung Adenocarcinoma withEGFRGenomic Alterations
肿瘤(癌症)患者之家