本研究旨在揭示幽门螺旋杆菌相关的炙症与免疫调节以及胃癌肿瘤微环境之间的关系。通过无监督聚类分析，在幽门螺旋杆菌相关的胃癌亚群中（GSE15459、GSE62254、GSE84437、GSE26253和TCGA-STAD），提取出与预后相关的炙症基因，识别出不同炙症表型和炙症基因组表型。采用GSVA方法量化关键基因集的激活程度，并通过ssGSEA和CIBERSORT方法估计免疫细胞浸润情况。通过主成分分析算法对炙症评分进行统计分析。评估了免疫应答（TMB和IPS）和基因突变的预测因子，并在两个抗PD-1治疗亚组中验证了炙症评分在预测免疫应答方面的有效性。 在1275例胃癌患者中建立了三种不同的炙症表型，分别对应着三种免疫表型：免疫炎症型、免疫贫穷型和免疫排除型。根据炙症评分，将患者分为高炙症评分组和低炙症评分组。低炙症评分表示有利的生存结果、增强的免疫应答和增加的突变频率。此外，低炙症评分患者在抗PD-1治疗中显示出更多的临床益处和延长的生存时间。 我们的研究揭示了炙症在胃癌免疫调节和肿瘤微环境的多样性和复杂性中所起的重要作用。在个体肿瘤中量化炙症评分可能有助于个体化制定更有效的免疫治疗策略。

Pyroptosis is a form of programmed cell death that is essential for immunity. Herein, this study was conducted to uncover the implication of pyroptosis in immunomodulation and tumor microenvironment (TME) in gastric cancer.Prognostic pyroptosis-related genes were extracted to identify different pyroptosis phenotypes and pyroptosis genomic phenotypes via unsupervised clustering analysis in the gastric cancer meta-cohort cohort (GSE15459, GSE62254, GSE84437, GSE26253 and TCGA-STAD). The activation of hallmark gene sets was quantified by GSVA and immune cell infiltration was estimated via ssGSEA and CIBERSORT. Through PCA algorithm, pyroptosis score was conducted. The predictors of immune response (TMB and IPS) and genetic mutations were evaluated. The efficacy of pyroptosis score in predicting immune response was verified in two anti-PD-1 therapy cohorts.Three different pyroptosis phenotypes with different prognosis, biological pathways and tumor immune microenvironment were established among 1275 gastric cancer patients, corresponding to three immune phenotypes: immune-inflamed, immune-desert, and immune-excluded. According to the pyroptosis score, patients were separated into high and low pyroptosis score groups. Low pyroptosis score indicated favorable survival outcomes, enhanced immune responses, and increased mutation frequency. Moreover, low pyroptosis score patients displayed more clinical benefits from anti-PD-1 and prolonged survival time.Our findings uncovered a nonnegligible role of pyroptosis in immunomodulation and TME multiformity and complicacy in gastric cancer. Quantifying the pyroptosis score in individual tumors may tailor more effective immunotherapeutic strategies.