Tumor Immunophenotyping‐Derived Signature Identifies Prognosis and Neoadjuvant Immunotherapeutic Responsiveness in Gastric Cancer
Jia‐Bin Wang, Qingzhu Qiu, Qiao‐Ling Zheng, Yajun Zhao, Yü Xu, Tao Zhang, S.-C. Wang, Quan Wang, Qinwen Jin, Yin‐Hua Ye, Ping Li, Jian‐Wei Xie, Jian‐Xian Lin, Jun Lu, Qi‐Yue Chen, Long‐Long Cao, Yinghong Yang, Chao‐Hui Zheng, Chang‐Ming Huang
Abstract
Abstract 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. IPS Low is characterized as immune‐activated, and IPS High 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 IPS Low 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.