新辅助免疫检查点抑制剂（ICI）治疗的有效性已在临床试验中得到证实，但适宜接受此疗法的患者仍未确定。先前的研究表明，肿瘤微环境（TME）主导免疫疗法，因此需要一种有效的TME分类策略。本研究在五个公共胃癌（GC）数据集（n = 1426）和一项内部测序数据集（n = 79）中确定了TME中的五种关键免疫表型相关分子（WARS，UBE2L6，GZMB，BATF2和LAG-3）。基于此，使用最小绝对收缩和选择算子（LASSO）Cox和randomSurvivalForest构建了一个GC免疫表型评分（IPS）。IPSLow表现为免疫激活状态，而IPSHigh则表现为免疫沉默状态。来自七个中心的数据（n = 1144）表明，IPS是一种可靠且独立的GC生物标志物，并优于AJCC分期。此外，IPSLow和联合阳性评分≥5的患者可能从新辅助抗PD-1疗法中受益。总之，IPS可以作为一种有用的免疫表型定量工具，以改善临床结果，并为实施GC患者的新辅助ICI疗法提供实用参考。©2023 The Authors.Advanced Science由Wiley-VCH GmbH出版。

The effectiveness of neoadjuvant immune checkpoint inhibitor (ICI) therapy is confirmed in clinical trials; however, the patients suitable for receiving this therapy remain unspecified. Previous studies have demonstrated that the tumor microenvironment (TME) dominates immunotherapy; therefore, an effective TME classification strategy is required. In this study, five crucial immunophenotype-related molecules (WARS, UBE2L6, GZMB, BATF2, and LAG-3) in the TME are determined in five public gastric cancer (GC) datasets (n = 1426) and an in-house sequencing dataset (n = 79). Based on this, a GC immunophenotypic score (IPS) is constructed using the least absolute shrinkage and selection operator (LASSO) Cox, and randomSurvivalForest. IPSLow is characterized as immune-activated, and IPSHigh is immune-silenced. Data from seven centers (n = 1144) indicate that the IPS is a robust and independent biomarker for GC and superior to the AJCC stage. Furthermore, patients with an IPSLow and a combined positive score of ≥5 are likely to benefit from neoadjuvant anti-PD-1 therapy. In summary, the IPS can be a useful quantitative tool for immunophenotyping to improve clinical outcomes and provide a practical reference for implementing neoadjuvant ICI therapy for patients with GC.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.