The assessment of programmed death-ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) has become increasingly important with the rise of immune checkpoint inhibitors (ICIs). However, challenges persist, including subjective interpretation and the unclear significance of staining intensity, as well as contrasting roles in tumoral and stromal regions. Our study enhances the understanding of PD-L1 in ESCCs by analyzing its expression in tumors and stroma with H-scores, highlighting its distinct clinicopathological impacts. In a retrospective cohort of 194 ESCC specimens from surgical resection, we quantified PD-L1 expression in tumoral and stromal compartments using H-scores, analyzing whole slide images with digital pathology analysis software. Kaplan–Meier analysis demonstrated that higher PD-L1 expression is significantly associated with improved postoperative overall survival (OS) and recurrence-free survival (RFS) in both tumoral and stromal areas. Multivariable analysis identified high tumoral PD-L1 expression as an independent prognostic factor for prolonged OS and RFS (HR = 0.47,p= 0.007; HR = 0.54,p= 0.022, respectively). In a separate analysis, high stromal PD-L1 expression was found to correlate with less advanced pathological stages and a prolonged response to cytotoxic chemotherapy, with no similar correlation found for ICI treatment response. This study reveals PD-L1’s contrasting role in the ESCC tumor immune microenvironment, impacting prognosis, tumor stage, and treatment response.
随着免疫检查点抑制剂(ICIs)的兴起,程序性死亡配体1(PD-L1)在食管鳞状细胞癌(ESCC)中的表达评估变得日益重要。然而,目前仍存在诸多挑战,包括主观判读、染色强度意义不明确,以及其在肿瘤区域和间质区域中相互矛盾的作用。本研究通过采用H评分分析PD-L1在肿瘤和间质中的表达,并强调其独特的临床病理学影响,从而加深了对PD-L1在ESCC中作用的理解。在一个包含194例手术切除ESCC标本的回顾性队列中,我们使用数字病理分析软件对全切片图像进行分析,通过H评分量化了PD-L1在肿瘤区域和间质区域的表达。Kaplan-Meier分析显示,无论是在肿瘤区域还是间质区域,较高的PD-L1表达均与改善的术后总生存期(OS)和无复发生存期(RFS)显著相关。多变量分析确定,肿瘤区域的高PD-L1表达是延长OS和RFS的独立预后因素(风险比HR = 0.47,p = 0.007;HR = 0.54,p = 0.022)。在另一项单独分析中,发现间质区域的高PD-L1表达与较低的病理分期以及对细胞毒性化疗的持久反应相关,但在ICI治疗反应中未发现类似关联。本研究揭示了PD-L1在ESCC肿瘤免疫微环境中的矛盾作用,影响预后、肿瘤分期及治疗反应。