本研究对消除异常细胞和重塑肿瘤微环境（TME）的细胞死亡模块进行了全面分析。基于 4 种细胞死亡预后基因对 490 名肺腺癌 (LUAD) 患者进行了共识分析。交叉法将这些LUAD样本分为5个细胞死亡风险（CDR）簇，并使用COX回归分析构建具有风险评分的CDR特征（CDRSig）。在不同的CDR簇中观察到TME表型、临床因素、基因组变异、放射敏感性和免疫治疗敏感性的显着差异。 CDRSig 中风险评分较高的患者往往被免疫排除或免疫沙漠，而风险评分较低的患者对放疗和免疫治疗更敏感。小鼠模型的结果表明，高危基因 PFKP 的强烈表达与放疗和抗 PD-L1 治疗时 CD8 T 细胞浸润较低有关。体外缺陷测定证实，PFKP 下调增强了 LUAD 细胞中 cGAS/STING 通路的激活和放射敏感性。总之，我们的研究最初进行了全面的细胞死亡分析，表明 CDR 模式在 TME 重编程中的重要性，并为 LUAD 个性化疗法提供新线索。© 2024。作者。

This study constructed a comprehensive analysis of cell death modules in eliminating aberrant cells and remodeling tumor microenvironment (TME). Consensus analysis was performed in 490 lung adenocarcinoma (LUAD) patients based on 4 types of cell death prognostic genes. Intersection method divided these LUAD samples into 5 cell death risk (CDR) clusters, and COX regression analysis were used to construct the CDR signature (CDRSig) with risk scores. Significant differences of TME phenotypes, clinical factors, genome variations, radiosensitivity and immunotherapy sensitivity were observed in different CDR clusters. Patients with higher risk scores in the CDRSig tended to be immune-excluded or immune-desert, and those with lower risk scores were more sensitive to radiotherapy and immunotherapy. The results from mouse model showed that intense expression of the high-risk gene PFKP was associated with low CD8+ T cell infiltration upon radiotherapy and anti-PD-L1 treatment. Deficient assays in vitro confirmed that PFKP downregulation enhanced cGAS/STING pathway activation and radiosensitivity in LUAD cells. In conclusion, our studies originally performed a comprehensive cell death analysis, suggesting the importance of CDR patterns in reprogramming TME and providing novel clues for LUAD personalized therapies.© 2024. The Author(s).