![]() The ICI-mediated antitumor response depends on the degree of infiltration of T cells capable of recognizing and killing tumor cells. Immune checkpoint inhibitor (ICI) therapy is primarily responsible for enhancing antitumor immunity by targeting regulatory pathways on T cells ( 5). It is therefore particularly important to increase the effectiveness and the proportion of patients who benefit from immunotherapy. However, the overall objective response rate with immunotherapy is low, the efficiency of third-line immunotherapy is not high, and patients have short progression-free survival ( 4). Immunotherapy can provide some survival benefits for some patients and maintain a sustained treatment effect for a long period. With the accumulation of evidence based on immunotherapy in advanced GC, the Chinese Society of Clinical Oncology and the European Society for Medical Oncology have adopted immunotherapy as the recommended third-line treatment for advanced GC ( 3). The current status of treatment for patients with advanced GC is not optimistic, the efficacy of chemotherapy has reached a bottleneck, and different degrees of resistance (primary and acquired) are encountered during targeted therapy, which remain a major obstacle to clinical targeted therapy ( 2), resulting in the current treatment options for GC being quite limited. Therefore, to improve the survival rate of GC, more effective tumor molecular subtypes and prognostic markers need to be developed. However, two-thirds of patients are already in a progressive stage at the time of initial treatment, and the 5-year survival rate is still less than 30%, even when treated with a combination of mainly surgical treatments ( 1). In recent years, with the development of medical technology and improved treatment for GC, the diagnosis rate, survival time, and quality of life of early GC have all improved significantly. Gastric cancer (GC) is a common malignant tumor and the leading cause of death from malignant tumors worldwide. Taken together, this study first constructed and validated a prognostic ICD-related signature to predict the survival and effect of immunotherapy in GC, which provided new insight for potent individualized immunotherapy strategies. These results suggest that ICD is closely associated with the prognosis and tumor immune microenvironment in GC. Notably, the risk score is a reliable predictor of the prognosis and immunotherapy outcome in GC, which was further validated in an immunohistochemistry assay. Then, we constructed an ICD-related risk signature, including IFNB1, IL6, LY96, and NT5E, using least absolute shrinkage and selection operator Cox regression analysis then, high- and low-risk groups could be clearly distinguished. The estimated scores, stromal scores, immune scores, tumor purity, and survival rate showed significant differences between the low and high ICD groups. In our study, two subgroups of patients were identified based on the data of 34 ICD-related genes extracted from The Cancer Genome Atlas database via consensus clustering. Therefore, we attempted to characterize the ICD-associated signature to stratify patients who could benefit from immunotherapy. Immunogenic cell death (ICD) was identified as a new form of regulated cell death that can activate adaptive immune responses and further promote immunotherapy efficacy. ![]() The majority of gastric cancer (GC) patients are in a progressive stage at the initial stage of treatment, and the overall response rate to immunotherapy remains unsatisfactory largely due to the lack of effective prognostic biomarkers. 3Institute of Clinical Pharmacology, Peking University, Beijing, China.2Department of Pharmacy, Peking University First Hospital, Beijing, China.1Department of General Surgery, Peking University First Hospital, Beijing, China. ![]() Bingqi Dong 1†, Yingchao Wu 1†, Junling Zhang 1†, Yanlun Gu 2,3, Ran Xie 2,3, Xu He 2,3, Xiaocong Pang 2,3*, Xin Wang 1* and Yimin Cui 2,3*
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