Correlation of tumor-infiltrating immune cells of melanoma with overall survival by immunogenomic analysis.

Correlation of tumor-infiltrating immune cells of melanoma with overall survival by immunogenomic analysis.
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通过免疫基因组分析观察黑色素瘤肿瘤浸润免疫细胞与总生存率的相关性

DOI:
10.1002/cam4.3466
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发表时间:
2020-11
期刊:
影响因子:
4
通讯作者:
Xu Q
Xu Q
中科院分区:
医学3区
文献类型:
--
作者:
Huang L;Chen H;Xu Y;Chen J;Liu Z;Xu Q

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不同类型的肿瘤浸润性免疫细胞不仅增强而且抑制黑色素瘤微环境中的抗肿瘤免疫。因此,提供黑色素瘤中肿瘤浸润免疫细胞的概述并探索免疫治疗的新策略至关重要。我们通过免疫、间质以及使用表达数据估计恶性肿瘤组织中的间质和免疫细胞(ESTIMATE)评分来分析黑色素瘤患者不同阶段的免疫状态。采用CIBERSORTx算法对471例黑色素瘤和324例健康组织中的免疫细胞类型进行了鉴定。此外,我们进行了基因集变异分析(GSVA),以确定肿瘤微环境中的差异调节途径。在黑色素瘤队列中,我们发现ESTIMATE和免疫评分与生存或肿瘤临床分期有关。在22种免疫细胞中,使用CIBERSORTx算法,CD 8 + T细胞、M2巨噬细胞和调节性T细胞(TcM)显示出显著差异。此外,GSVA确定了免疫细胞相关途径;原发性免疫缺陷途径、伊加的肠道免疫网络和TGF-β途径被确定为黑色素瘤微环境中CD 8 + T细胞、TcB和M2巨噬细胞中串扰的参与者。这些结果揭示了黑色素瘤中免疫细胞的细胞和分子特征,为选择免疫治疗的靶点和提高黑色素瘤治疗的疗效提供了方法。免疫疗法在黑色素瘤中显示出极好的反应,而反应是低的。然而,肿瘤浸润免疫细胞的分子机制尚未被探索。在这项研究中,我们发现较高的ESTIMATE和免疫评分与黑色素瘤患者的临床分期相关,并且还过滤了免疫细胞之间的串扰。我们的工作揭示了黑色素瘤的免疫细胞和分子特征,为选择促进免疫治疗效果的靶点提供了方法。
Different types of tumor‐infiltrating immune cells not only augment but also dampen antitumor immunity in the microenvironment of melanoma. Therefore, it is critical to provide an overview of tumor‐infiltrating immune cells in melanoma and explore a novel strategy for immunotherapies. We analyzed the immune states of different stages in melanoma patients by the immune, stromal, and estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) scores. Immune cell types were identified by the estimating relative subsets of RNA transcripts (CIBERSORTx) algorithm in 471 melanoma and 324 healthy tissues. Moreover, we performed a gene set variation analysis (GSVA) to determine the differentially regulated pathways in the tumor microenvironment. In melanoma cohorts, we found that ESTIMATE and immune scores were involved in survival or tumor clinical stage. Among the 22 immune cells, CD8+ T cells, M2 macrophages, and regulatory T cells (Tregs) showed significant differences using the CIBERSORTx algorithm. Furthermore, GSVA identified the immune cell‐related pathways; the primary immunodeficiency pathway, intestinal immune network for IgA, and TGF‐β pathways were identified as participants of the crosstalk in CD8+ T cells, Tregs, and M2 macrophages in the melanoma microenvironment. These results reveal the cellular and molecular characteristics of immune cells in melanoma, providing a method for selecting targets of immunotherapies and promoting the efficacy of therapies for the treatment of melanoma. Immunotherapy has shown excellent responses in melanoma, while the reaction is low. However, the molecular mechanisms of tumor infiltrated immune cells have not been explored. In this study, we found that higher ESTIMATE and immune scores were associated with a clinical‐stage in melanoma patients and also filtered the crosstalks between cells that immune cells. Our work revealed the immune cellular and molecular characteristics of melanoma, providing a method for selecting targets promoting immunotherapy efficacy.
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