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一种评估肝细胞癌肿瘤免疫微环境及预测预后的非侵入性方法

A Noninvasive Approach to Evaluate Tumor Immune Microenvironment and Predict Outcomes in Hepatocellular Carcinoma.

作者信息

Wu Jianmin, Liu Wanmin, Qiu Xinyao, Li Jing, Song Kairong, Shen Siyun, Huo Lei, Chen Lu, Xu Mingshuang, Wang Hongyang, Jia Ningyang, Chen Lei

机构信息

Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, 200438 China.

The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438 China.

出版信息

Phenomics. 2023 Dec 8;3(6):549-564. doi: 10.1007/s43657-023-00136-8. eCollection 2023 Dec.


DOI:10.1007/s43657-023-00136-8
PMID:38223688
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10781918/
Abstract

UNLABELLED: It is widely recognized that tumor immune microenvironment (TIME) plays a crucial role in tumor progression, metastasis, and therapeutic response. Despite several noninvasive strategies have emerged for cancer diagnosis and prognosis, there are still lack of effective radiomic-based model to evaluate TIME status, let alone predict clinical outcome and immune checkpoint inhibitor (ICIs) response for hepatocellular carcinoma (HCC). In this study, we developed a radiomic model to evaluate TIME status within the tumor and predict prognosis and immunotherapy response. A total of 301 patients who underwent magnetic resonance imaging (MRI) examinations were enrolled in our study. The intra-tumoral expression of 17 immune-related molecules were evaluated using co-detection by indexing (CODEX) technology, and we construct Immunoscore (IS) with the least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression method to evaluate TIME. Of 6115 features extracted from MRI, five core features were filtered out, and the Radiomic Immunoscore (RIS) showed high accuracy in predicting TIME status in testing cohort (area under the curve = 0.753). More importantly, RIS model showed the capability of predicting therapeutic response to anti-programmed cell death 1 (PD-1) immunotherapy in an independent cohort with advanced HCC patients (area under the curve = 0.731). In comparison with previously radiomic-based models, our integrated RIS model exhibits not only higher accuracy in predicting prognosis but also the potential guiding significance to HCC immunotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-023-00136-8.

摘要

未标注:肿瘤免疫微环境(TIME)在肿瘤进展、转移及治疗反应中发挥着关键作用,这一点已得到广泛认可。尽管已出现多种用于癌症诊断和预后评估的非侵入性策略,但仍缺乏有效的基于影像组学的模型来评估TIME状态,更不用说预测肝细胞癌(HCC)的临床结局和免疫检查点抑制剂(ICI)反应了。在本研究中,我们开发了一种影像组学模型来评估肿瘤内的TIME状态,并预测预后和免疫治疗反应。共有301例接受磁共振成像(MRI)检查的患者纳入我们的研究。使用索引编码技术(CODEX)联合检测评估17种免疫相关分子的肿瘤内表达,并采用最小绝对收缩和选择算子(LASSO)算法及Cox回归方法构建免疫评分(IS)以评估TIME。从MRI提取的6115个特征中筛选出5个核心特征,影像组学免疫评分(RIS)在测试队列中预测TIME状态时显示出较高的准确性(曲线下面积=0.753)。更重要的是,RIS模型在一个晚期HCC患者的独立队列中显示出预测抗程序性细胞死亡蛋白1(PD - 1)免疫治疗反应的能力(曲线下面积=0.731)。与先前基于影像组学的模型相比,我们的综合RIS模型不仅在预测预后方面具有更高的准确性,而且对HCC免疫治疗具有潜在的指导意义。 补充信息:在线版本包含可在10.1007/s43657 - 023 - 00136 - 8获取的补充材料。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b15a/10781918/0e3e5f2f2b0d/43657_2023_136_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b15a/10781918/ea1cf3746527/43657_2023_136_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b15a/10781918/ea5a12789b2e/43657_2023_136_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b15a/10781918/f8d46a204e7b/43657_2023_136_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b15a/10781918/59bd7b8bcc4f/43657_2023_136_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b15a/10781918/0e3e5f2f2b0d/43657_2023_136_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b15a/10781918/ea1cf3746527/43657_2023_136_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b15a/10781918/ea5a12789b2e/43657_2023_136_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b15a/10781918/f8d46a204e7b/43657_2023_136_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b15a/10781918/59bd7b8bcc4f/43657_2023_136_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b15a/10781918/0e3e5f2f2b0d/43657_2023_136_Fig5_HTML.jpg

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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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J Hepatocell Carcinoma. 2025-4-30

[10]
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本文引用的文献

[1]
Single-cell dissection of cervical cancer reveals key subsets of the tumor immune microenvironment.

EMBO J. 2023-8-15

[2]
Intratumoral Abundance of M2-Macrophages is Associated With Unfavorable Prognosis and Markers of T-Cell Exhaustion in Small Cell Lung Cancer Patients.

Mod Pathol. 2023-10

[3]
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Cancer Cell. 2023-3-13

[4]
Ongoing involvers and promising therapeutic targets of hepatic fibrosis: The hepatic immune microenvironment.

Front Immunol. 2023

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Bispecific PD1-IL2v and anti-PD-L1 break tumor immunity resistance by enhancing stem-like tumor-reactive CD8 T cells and reprogramming macrophages.

Immunity. 2023-1-10

[6]
CD8A as a Prognostic and Immunotherapy Predictive Biomarker Can Be Evaluated by MRI Radiomics Features in Bladder Cancer.

Cancers (Basel). 2022-10-5

[7]
Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma.

Gastroenterology. 2023-1

[8]
Noninvasive imaging of the tumor immune microenvironment correlates with response to immunotherapy in gastric cancer.

Nat Commun. 2022-8-30

[9]
Inflammatory Microenvironment in Early Non-Small Cell Lung Cancer: Exploring the Predictive Value of Radiomics.

Cancers (Basel). 2022-7-8

[10]
Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors.

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