TIP: A Web Server for Resolving Tumor Immunophenotype Profiling

Xu, Liwen; Deng, Chunyu; Pang, Bo; Zhang, Xinxin; Liu, Wei; Liao, Gaoming; Yuan, Huating; Peng, Cheng; Li, Feng; Long, Zhilin; Yan, Min; Zhao, Tingting; Xiao, Yun; Li, Xia

doi:10.1158/0008-5472.can-18-0689

Cited by 397 publications

(375 citation statements)

References 28 publications

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“…Genes signatures were download from Tracking Tumor Immunophenotype website (http://biocc. hrbmu.edu.cn/TIP/index.jsp) (14). As show in Figures 7A,B, genes involved in the negative regulation of the Cancer-Immunity Cycle were mostly upregulated in the high hypoxia risk group, indicating that patients in this group have low activities of the processes.…”

Section: High Hypoxia Risk Score Indicates An Immunosuppressive Micromentioning

confidence: 84%

Characterization of Hypoxia Signature to Evaluate the Tumor Immune Microenvironment and Predict Prognosis in Glioma Groups

et al. 2020

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Glioma groups, including lower-grade glioma (LGG) and glioblastoma multiforme (GBM), are the most common primary brain tumor. Malignant gliomas, especially glioblastomas, are associated with a dismal prognosis. Hypoxia is a driver of the malignant phenotype in glioma groups; it triggers a cascade of immunosuppressive processes and malignant cellular responses (tumor progression, anti-apoptosis, and resistance to chemoradiotherapy), which result in disease progression and poor prognosis. However, approaches to determine the extent of hypoxia in the tumor microenvironment are still unclear. Here, we downloaded 575 LGG patients and 354 GBM patients from Chinese Glioma Genome Atlas (GGGA), and 530 LGG patients and 167 GBM patients from The Cancer Genome Atlas (TCGA) with RNA sequence and clinicopathological data. We developed a hypoxia risk model to reflect the immune microenvironment in glioma and predict prognosis. High hypoxia risk score was associated with poor prognosis and indicated an immunosuppressive microenvironment. Hypoxia signature significantly correlated with clinical and molecular features and could serve as an independent prognostic factor for glioma patients. Moreover, Gene Set Enrichment Analysis showed that gene sets associated with the high-risk group were involved in carcinogenesis and immunosuppression signaling. In conclusion, we developed and validated a hypoxia risk model, which served as an independent prognostic indicator and reflected overall immune response intensity in the glioma microenvironment.

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Section: High Hypoxia Risk Score Indicates An Immunosuppressive Micromentioning

confidence: 84%

Characterization of Hypoxia Signature to Evaluate the Tumor Immune Microenvironment and Predict Prognosis in Glioma Groups

et al. 2020

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“…As several of the immune cell types which were inversely correlated with ZEB1 are known to activate the immune response, we dissected the immune activity profile of the breast cancer tumor samples using the Tumor ImmunoPhenotype server algorithm (TIP) 30 . Like xCELL, TIP uses gene sets to evaluate immune activity in bulk tumor samples.…”

Section: Resultsmentioning

confidence: 99%

“…Like xCELL, TIP uses gene sets to evaluate immune activity in bulk tumor samples. However, instead of evaluating by cell type, TIP estimates the relative activity of different stages of the immune response, from tumor-antigen presentation to tumor cell killing by immune cells 30 . TIP scores were downloaded and compared with ZEB1 expression by partial correlation analysis.…”

Section: Resultsmentioning

confidence: 99%

A stroma-corrected ZEB1 transcriptional signature is inversely associated with antitumor immune activity in breast cancer

Block

Dyson

Campeanu

et al. 2019

Sci Rep

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The epithelial-to-mesenchymal transition (EMT) is an essential developmental process which can be hijacked by cancer cells, leading to enhanced metastasis and chemoresistance in experimental models. Recent studies have linked gene expression of EMT-associated gene signatures to increased inflammatory immune response in multiple cancer types. However, these studies did not account for the potential confounding effects of gene expression by tumor-infiltrating mesenchymal stromal cells. In this study, we comprehensively dissect the associations between multiple EMT transcription factors and EMT markers with stromal and immune tumor infiltration. We find that EMT-related genes are highly correlated with intratumoral stromal cell abundance and identify a specific relationship between stroma-corrected ZEB1 expression and decreased immune activity in multiple cancer types. We derive a stroma-corrected ZEB1-activated transcriptional signature and demonstrate that this signature includes several known inhibitors of inflammation, including BMPR2. Finally, multivariate survival analysis reveals that ZEB1 and its expression signature are significantly associated with reduced overall survival in breast cancer patients. In conclusion, this study identifies a novel association between stroma-adjusted ZEB1 expression and tumor immune activity and addresses the critical issue of confounding between EMT-associated genes and tumor stromal content.

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“…However, in glioma, the high-risk group had signi cantly higher immune cell enrichment than the low-risk group, but the prognosis was worse than that of the low-risk group, indicating that there may be other immunosuppressive mechanisms in the high-risk group. To explore this, we rst detected the expression of cancer-immunity cycle inhibitors in the two groups (38). The expression levels of most cancer-immunity cycle inhibitors in the high-risk group were obviously higher than those in the low-risk group in the TCGA, CGGA, and GSE16011 (Fig.…”

Section: Vitamin-related Signature Indicates An Immunosuppressive Micmentioning

confidence: 99%

Development of A Vitamin-related Gene Signature to Predict the Immune Characteristics and Prognosis of Glioma

Zhang

Liang

Guan

et al. 2020

Preprint

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Background: Vitamins not only play a pivotal role in maintaining homeostasis of the body, but also have complex impacts on the occurrence and progression of tumors. However, the effects of vitamins on glioma and the underlying mechanism have not been fully elucidated. Methods: Vitamin -related genes were extracted from the Molecular Signature Database v7.1 (MSigDB). The overlapping overall survival (OS)-related genes in The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and GSE16011 cohorts screened out by univariate COX regression analysis were utilized to construct a risk model based on the TCGA cohort via random survival forest analysis and multivariate COX regression analysis. The powerful prognostic predictive potential of the vitamin-related risk signature was verified by Kaplan–Meier survival analysis and receiver operating characteristic (ROC) analysis in the three datasets. The ssGSEA method of the GSVA package was used for functional enrichment and immune cell component analyses. ESTIMATE score analysis was used for auxiliary analysis of glioma immune characteristics. A nomogram was constructed and assessed based on the TCGA dataset.Results: The vitamin-related six-gene (POSTN, IRX5, EEF2, RAB27A, MDM2, and ENO1) risk signature constructed based on the TCGA dataset accurately predicted the outcomes of glioma patients and credibly distinguished between different levels and molecular subtypes of glioma in the TCGA, CGGA, and GSE16011 cohorts. Gliomas with high risk scores exhibited high immune scores, low tumor purity, and immunosuppressive features. The nomogram constructed by combining the vitamin-related risk signature and clinicopathological factors precisely predicted the 1-, 3-, and 5-year OS of glioma patients.Conclusions: Our study revealed that the vitamin-related six-gene risk signature, as an independent prognostic factor, could accurately distinguish the grade, molecular subtype, and immune characteristics of glioma.

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TIP: A Web Server for Resolving Tumor Immunophenotype Profiling

Cited by 397 publications

References 28 publications

Characterization of Hypoxia Signature to Evaluate the Tumor Immune Microenvironment and Predict Prognosis in Glioma Groups

Characterization of Hypoxia Signature to Evaluate the Tumor Immune Microenvironment and Predict Prognosis in Glioma Groups

A stroma-corrected ZEB1 transcriptional signature is inversely associated with antitumor immune activity in breast cancer

Development of A Vitamin-related Gene Signature to Predict the Immune Characteristics and Prognosis of Glioma

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