Clinical Research on Predicting the Efficacy of Immunotherapy Combined with Chemotherapy in Esophageal Squamous Cell Carcinoma Based on PD-L1 Expression and TILs Infiltration Typing

目的：评估PD-L1表达(CPS)和TILs密度对ESCC免疫联合化疗疗效的预测能力，验证TIME分型体系，探索其临床转化潜力。方法：回顾性分析2017年1月至2024年12月青岛大学附属医院收治的238例初治ESCC患者，均接受PD-1/PD-L1抑制剂联合化疗。通过免疫组化检测PD-L1表达(CPS)和TILs密度，基于PD-L1 (CPS ≥ 10)和TILs (≥20%)将TIME分为四型(PD-L1+/TIL+、PD-L1+/TIL−、PD-L1−/TIL+、PD-L1−/TIL−)。采用Fisher-Freeman-Halton检验等统计学方法评估各型ORR差异，并用Kaplan-Meier法及Log-rank检验分析生存数据。结果：PD-L1阳性(CPS ≥ 10)和TILs高浸润(≥20%)患者ORR更高(PD-L1+ vs. PD-L1−: 34.9% vs. 20.8%, P = 0.030; TIL+ vs. TIL−: 42.7% vs. 7.4%, P +/TIL+) ORR最高(44.55%)，显著优于其他亚型(vs. IV型：P −/TIL−) ORR最低(12.50%)。生存分析显示，II型中位OS (37.4个月)和PFS (23.1个月)显著优于I型和IV型(Log-rank P Objective: To assess the predictive value of PD-L1 expression (CPS) and TILs density for ICI-chemotherapy efficacy in ESCC patients and validate the TIME classification system. Methods: Retrospective analysis of 238 treatment-naïve ESCC patients receiving PD-1/PD-L1 inhibitors combined with chemotherapy from January 2017 to December 2024. PD-L1 (CPS) and TILs density were evaluated by immunohistochemistry. TIME was classified into four subtypes based on PD-L1 (CPS ≥ 10) and TILs (≥20%). ORR differences were assessed using Fisher-Freeman-Halton test, and survival data were analyzed using Kaplan-Meier and Log-rank tests. Results: PD-L1 positivity (CPS ≥ 10) and high TILs infiltration (≥20%) were associated with higher ORR (PD-L1+ vs. PD-L1−: 34.9% vs. 20.8%, P = 0.030; TIL+ vs. TIL−: 42.7% vs. 7.4%, P +/TIL+) had the highest ORR (44.55%) which was significantly better than other subtypes (vs. Type IV: P −/TIL−) had the lowest ORR (12.50%). Survival analysis showed that Type II had significantly longer median OS (37.4 months) and PFS (23.1 months) compared with Type I and Type IV (Log-rank P < 0.001). Conclusion: TIME classification effectively predicts the efficacy and survival outcomes of ICI-chemotherapy in ESCC patients. Type II represents the ideal beneficiary population. Strategies to reverse immune suppression should be explored for Type I and Type IV.