免疫原性细胞死亡（ICD）是一种特定类型的调节性细胞死亡（RCD），它诱导对死亡细胞抗原的适应性免疫。ICD因其在肿瘤微环境重编程和免疫疗法中的潜在作用，受到越来越多的关注。然而，ICD相关特征与胃腺癌（STAD）预后、免疫细胞浸润和免疫疗法之间的关系尚不清楚。通过共识聚类将患者分为不同的ICD相关亚型。系统评估不同ICD相关亚型之间的预后、肿瘤微环境（TME）和免疫检查点表达的差异。此外，我们构建了一个ICD相关基因风险评分（ICDRS）。我们系统分析了胃癌ICDRS与预后、TME、免疫疗法反应和药物敏感性之间的相关性。此外，我们通过体外实验探讨了TGM2在促进胃癌进展中的作用。我们通过共识聚类确定了三个与ICD相关的亚型。ICD基因在B族中高度表达。与其他两个亚型相比，B族的预后较好，免疫应答信号活性较高，有大量免疫细胞浸润和较低的肿瘤纯度。免疫检查点（ICP）和人类白细胞抗原（HLA）相关基因在B族中也高度表达。此外，我们发现ICDRS是预测STAD预后和免疫效果的有效指标。低ICDRS组具有良好预后、高肿瘤突变负荷（TMB）、高微卫星不稳定性（MSI）和对免疫疗法的敏感性，而高ICDRS组易于免疫逃逸和免疫疗法抵抗。此外，我们发现下调TGM2基因可以通过体外实验抑制胃癌细胞的增殖和迁移。我们的研究发现基于ICD特征的模型有助于阐明STAD的TME特征，并对评估STAD患者的预后和免疫疗法反应具有重要临床意义。TGM2在STAD的进展中起重要作用，表明TGM2可以作为STAD治疗的新靶点。（摘自：2023年，作者（们）在Springer Science+Business Media, LLC，Springer Nature的独家许可下发表）

The immunogenic cell death (ICD) is a specific type of regulatory cell death (RCD), which induces adaptive immunity against antigens of dead cells. ICDs have received increasing attention for their potential role in tumor microenvironment reprogramming and immunotherapy. However, the relationship between ICD-related features and stomach adenocarcinoma (STAD) prognosis, immune cell infiltration and immunotherapy remains unclear. Patients were divided into different ICD-related subtypes by consensus clustering. The differences in prognosis, Tumor microenvironment (TME), and immune checkpoint expression between different ICD-related subtypes were systematically assessed. Additionally, we constructed an ICD-related gene risk score (ICDRS). We systematically analyzed the correlation between ICDRS and prognosis, TME, immunotherapy response and drug sensitivity of gastric cancer. In addition, we explored the role of TGM2 in promoting gastric cancer progression through in vitro experiments. We identified three ICD-associated subtypes by consensus clustering. The ICD gene was highly expressed in Cluster B. Compared with the other two subtypes, Cluster B had better prognosis, higher immune response signaling activity, massive immune cell infiltration and lower tumor purity. Immune checkpoint (ICP) and human leukocyte antigen (HLA) related genes were also highly expressed in Cluster B. In addition, we found that ICDRS is an effective indicator for predicting the prognosis and immune efficacy of STAD. The low ICDRS group has the characteristics of good prognosis, high tumor mutation burden (TMB), high microsatellite instability (MSI), and sensitivity to immunotherapy, while the high ICDRS group is prone to immune escape and immunotherapy resistance. In addition, we found that down-regulating TGM2 gene can inhibit the proliferation and migration of gastric cancer cells through in vitro experiments. Our study found that the model based on ICD features is helpful to clarify the TME characteristics of STAD, and has important clinical significance for evaluating the prognosis and immunotherapy response of STAD patients. TGM2 plays an important role in the progression of STAD, suggesting that TGM2 can be used as a new target for the treatment of STAD.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.