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Abstract：
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.
摘要：
随着免疫检查点抑制剂（ICIs）的兴起，评估食管鳞状细胞癌（ESCC）中程序性死亡配体1（PD-L1）的表达变得越来越重要。然而,挑战依然存在,包括主观解释和染色强度的不明确意义，以及在肿瘤和基质区域的对比作用。我们的研究通过分析PD-L1在肿瘤和基质中的表达与H评分，增强了对ESCCs中PD-L1的理解。突出了其独特的临床病理影响。在来自手术切除的194例ESCC标本的回顾性队列中，我们使用H评分量化肿瘤和基质区室中的PD-L1表达，用数字病理分析软件分析整个幻灯片图像。Kaplan-Meier分析表明，较高的PD-L1表达与肿瘤和基质区域的术后总生存期（OS）和无复发生存期（RFS）的改善显着相关。多变量分析确定肿瘤PD-L1高表达是OS和RFS延长的独立预后因素（分别为HR=0.47，p=0.007；HR=0.54，p=0.022）。在单独的分析中，发现高基质PD-L1表达与较不晚期的病理阶段和对细胞毒性化疗的长期反应相关，与ICI治疗反应没有类似的相关性。本研究揭示了PD-L1在ESCC肿瘤免疫微环境中的对比作用，影响预后，肿瘤分期,和治疗反应。
