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免疫原性细胞死亡相关生物标志物分类可预测胰腺导管腺癌的预后和免疫治疗疗效。

Immunogenic cell death-associated biomarkers classification predicts prognosis and immunotherapy efficacy in pancreatic ductal adenocarcinoma.

作者信息

Peng Wenguang, Yang Jiarui, Xia Long, Qian Xiangjun, Long Guojie, Zhang Hao, Xie Jiancong, Zhao Junzhang, Zhang Lei, Pan Weidong

机构信息

Department of Pancreatic-Hepato-Biliary-Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Department of Hepatobiliary-Pancreatic-Splenic Surgery, Inner Mongolia Autonomous Region People's Hospital, Hohhot, China.

出版信息

Front Oncol. 2023 Mar 30;13:1178966. doi: 10.3389/fonc.2023.1178966. eCollection 2023.

Abstract

INTRODUCTION

Immunogenic cell death (ICD) is a sort of regulated cell death (RCD) sufficient to trigger an adaptive immunological response. According to the current findings, ICD has the capacity to alter the tumor immune microenvironment by generating danger signals or damage-associated molecular patterns (DAMPs), which may contribute in immunotherapy. It would be beneficial to develop ICD-related biomarkers that classify individuals depending on how well they respond to ICD immunotherapy.

METHODS AND RESULTS

We used consensus clustering to identify two ICD-related groupings. The ICD-high subtype was associated with favorable clinical outcomes, significant immune cell infiltration, and powerful immune response signaling activity. In addition, we developed and validated an ICD-related prognostic model for PDAC survival based on the tumor immune microenvironment. We also collected clinical and pathological data from 48 patients with PDAC, and patients with high EIF2A expression had a poor prognosis. Finally, based on ICD signatures, we developed a novel PDAC categorization method. This categorization had significant clinical implications for determining prognosis and immunotherapy.

CONCLUSION

Our work emphasizes the connections between ICD subtype variations and alterations in the immune tumor microenvironment in PDAC. These findings may help the immune therapy-based therapies for patients with PDAC. We also created and validated an ICD-related prognostic signature, which had a substantial impact on estimating patients' overall survival times (OS).

摘要

引言

免疫原性细胞死亡(ICD)是一种程序性细胞死亡(RCD),足以引发适应性免疫反应。根据目前的研究结果,ICD能够通过产生危险信号或损伤相关分子模式(DAMPs)来改变肿瘤免疫微环境,这可能有助于免疫治疗。开发与ICD相关的生物标志物,根据个体对ICD免疫治疗的反应程度进行分类,将是有益的。

方法与结果

我们使用共识聚类法识别出两个与ICD相关的分组。ICD高亚型与良好的临床结果、显著的免疫细胞浸润和强大的免疫反应信号活性相关。此外,我们基于肿瘤免疫微环境开发并验证了一种用于预测胰腺导管腺癌(PDAC)生存的与ICD相关的预后模型。我们还收集了48例PDAC患者的临床和病理数据,EIF2A表达高的患者预后较差。最后,基于ICD特征,我们开发了一种新的PDAC分类方法。这种分类对于确定预后和免疫治疗具有重要的临床意义。

结论

我们的工作强调了ICD亚型变异与PDAC肿瘤免疫微环境改变之间的联系。这些发现可能有助于为PDAC患者提供基于免疫治疗的方案。我们还创建并验证了一个与ICD相关的预后特征,这对估计患者的总生存时间(OS)有重大影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/728b/10098015/89ff7007a83f/fonc-13-1178966-g001.jpg

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