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探究三阴性乳腺癌的免疫原性细胞死亡依赖性亚型及预后标志物

Investigating the Immunogenic Cell Death-Dependent Subtypes and Prognostic Signature of Triple-Negative Breast Cancer.

作者信息

Shi Youyang, Wu Yuanyuan, Li Feifei, Jiang Kexin, Fang Xiaofang, Wang Yu, Song Xiaoyun, Wang Rui, Chen Lixin, Zheng Jinzhou, Wu Chunyu, Qin Yuenong, Liu Xiaofei, Liu Sheng

机构信息

Breast Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Wanping South Road, 725, Shanghai, 200033 China.

First Clinical College, Shandong University of Traditional Chinese Medicine, No. 16369, Jingshi Road, Lixia District, Jinan, 250011 Shandong China.

出版信息

Phenomics. 2024 Mar 13;4(1):34-45. doi: 10.1007/s43657-023-00133-x. eCollection 2024 Feb.

Abstract

UNLABELLED

Recently, immunotherapy has emerged as a promising and effective method for treating triple-negative breast cancer (TNBC). However, challenges still persist. Immunogenic cell death (ICD) is considered a prospective treatment and potential combinational treatment strategy as it induces an anti-tumor immune response by presenting the antigenic epitopes of dead cells. Nevertheless, the ICD process in TNBC and its impact on disease progression and the response to immunotherapy are not well understood. In this study, we observed dysregulation of the ICD process and verified the altered expression of prognostic ICD genes in TNBC through quantitative real-time polymerase chain reaction (qRT-PCR) analysis. To investigate the potential role of the ICD process in TNBC progression, we determined the ICD-dependent subtypes, and two were identified. Analysis of their distinct tumor immune microenvironment (TIME) and cancer hallmark features revealed that Cluster 1 and 2 corresponded to the immune "cold" and "hot" phenotypes, respectively. In addition, we constructed the prognostic signature ICD score of TNBC patients and demonstrated its clinical independence and generalizability. The ICD score could also serve as a potential biomarker for immune checkpoint blockade and may aid in the identification of targeted effective agents for individualized clinical strategies.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s43657-023-00133-x.

摘要

未标注

最近,免疫疗法已成为治疗三阴性乳腺癌(TNBC)的一种有前景且有效的方法。然而,挑战依然存在。免疫原性细胞死亡(ICD)被认为是一种前瞻性治疗和潜在的联合治疗策略,因为它通过呈现死亡细胞的抗原表位来诱导抗肿瘤免疫反应。然而,TNBC中的ICD过程及其对疾病进展和免疫治疗反应的影响尚未得到充分了解。在本研究中,我们观察到ICD过程的失调,并通过定量实时聚合酶链反应(qRT-PCR)分析验证了TNBC中预后ICD基因的表达变化。为了研究ICD过程在TNBC进展中的潜在作用,我们确定了依赖ICD的亚型,并识别出两种。对其不同的肿瘤免疫微环境(TIME)和癌症特征的分析表明,簇1和簇2分别对应免疫“冷”和“热”表型。此外,我们构建了TNBC患者的预后特征ICD评分,并证明了其临床独立性和普遍性。ICD评分还可作为免疫检查点阻断的潜在生物标志物,并可能有助于识别用于个体化临床策略的靶向有效药物。

补充信息

在线版本包含可在10.1007/s43657-023-00133-x获取的补充材料。

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