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System for evaluating immunotherapy reactivity of glioblastoma patient based on ferroptosis level and analysis method

A technology for glioblastoma and immunotherapy, applied in the analysis of two-dimensional or three-dimensional molecular structure, biochemical equipment and methods, biostatistics, etc., and can solve problems such as neglect effects

Pending Publication Date: 2021-09-21
吴安华
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, current research on ferroptosis mainly focuses on tumor cells, ignoring its role in the tumor immune microenvironment

Method used

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  • System for evaluating immunotherapy reactivity of glioblastoma patient based on ferroptosis level and analysis method
  • System for evaluating immunotherapy reactivity of glioblastoma patient based on ferroptosis level and analysis method
  • System for evaluating immunotherapy reactivity of glioblastoma patient based on ferroptosis level and analysis method

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Embodiment 1

[0040] The relationship between ferroptosis score and clinical indicators was studied. We investigated the role of ferroptosis score in glioma progression in the CGGA database, and analyzed the relationship between ferroptosis score and prognosis using Kaplan-Meier curves and log-rank. Survival curves showed that patients with high iron death scores had lower overall survival compared with patients with low iron death scores (eg figure 1 shown in A). After classification by grade, higher ferroptosis scores in the most aggressive glioblastomas still predicted poorer overall survival (eg, figure 1 shown in B). We are again in TCGA (such as figure 1 shown in C) and GSE16011 (as shown in figure 1 The same analysis was performed on the database shown in D) and the same conclusions were reached. Overall, glioblastoma with high ferroptosis levels had lower overall survival.

Embodiment 2

[0042] The relationship between ferroptosis score and immune infiltration was studied. We selected genes highly correlated with ferroptosis score in glioblastoma (Pearson correlation | r | ≥ 0.6) for Gene Ontology (GO) analysis. In addition to signaling pathways related to cell death, the ferroptosis score is also related to various immune system processes (such as figure 2 shown in A). Glioblastoma patients with high ferroptosis scores also showed enrichment status in multiple immune-related pathways (such as figure 2 Shown in B), which further illustrates that ferroptosis plays an important role in the regulation of tumor immunity. In order to further explore the relationship between ferroptosis and tumor immunity, we performed TIP analysis (http: / / biocc.hrbmu.edu.cn / TIP / index.jsp). Taking all the expression data of samples in the CGGA database as input, two existing algorithms (ssGSEA and CIBERSORT) were systematically integrated, through the analysis of tumor cell ant...

Embodiment 3

[0046] To study the relationship between ferroptosis and sensitivity to immunotherapy. To test whether inhibition of ferroptosis could sensitize glioblastoma to immunoregulatory point-targeted therapy (anti-PD-L1 therapy), we used anti-PD-L1 antibody alone, alone in a mouse model of orthotopic tumorigenesis. Mice were treated with the ferroptosis inhibitor ferrostatin-1 and a combination of an anti-PD-L1 antibody and the ferroptosis inhibitor ferrostatin-1. Mice treated with a combination of Ferrostatin-1 and an anti-PD-L1 antibody had the longest survival time and the smallest tumor size. Anti-PD-L1 monotherapy slightly prolongs survival time and reduces tumor size in mice (eg Image 6 shown in A). IHC staining showed that combination therapy significantly increased CD3+ and CD8+ T cells (eg Image 6 shown in B). Next, we performed flow cytometry to evaluate the tumor-killing ability of CD8+ T cells. Combination therapy significantly increased the infiltration of CD8+IFN...

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Abstract

The invention discloses a system for evaluating immunotherapy reactivity of a glioblastoma patient based on a ferroptosis level and an analysis method, and belongs to the technical field of immunotherapy reactivity analysis. The system for evaluating the immunotherapy reactivity of the glioblastoma patient based on the ferroptosis level comprises an input module, an analysis module and an output module. The system for evaluating the immunotherapy reactivity of the glioma patients based on the ferroptosis level is established by summarizing data of 1750 glioma patients from four independent databases, and by calculating and comparing the ferroptosis level, the malignant development of glioma, the length of prognosis lifetime, the anti-tumor immunity and the reactivity of immunotherapy can be predicted. Meanwhile, the system can predict whether the immunotherapy effect can be improved by inhibiting the ferroptosis level or not, and auxiliary guidance can be provided for clinical analysis and application.

Description

technical field [0001] The invention relates to a system and analysis method for evaluating immunotherapy responsiveness of glioblastoma patients based on ferroptosis level, belonging to the technical field of immunotherapy responsiveness analysis. Background technique [0002] Emerging immunotherapies using immune checkpoint blockade (ICB, PD-1 / L1, and CTLA-4) have been approved for the treatment of a variety of solid cancers, including melanoma, non-small cell lung cancer, and bladder cancer. However, current clinical trials show that only 8% of glioma patients benefit from ICB treatment. Therefore, it is urgent to elucidate the mechanism of immune resistance, so as to provide a reasonable way to overcome the clinical dilemma of ICB treatment in glioma. Malignant glioma has the characteristics of complex microenvironmental components, and the median proportion of tumor cells in glioma tissue is only 74%. During glioma progression, glioma cells selectively enrich immune r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G16B40/00G16B15/30G16B25/00G16B50/30G16H10/20G16H50/20G16H70/40C12Q1/6869
CPCG16B40/00G16B15/30G16B25/00G16B50/30G16H10/20G16H50/20G16H70/40C12Q1/6869C12Q2535/122C12Q2537/165
Inventor 刘天奇朱晨陈新程文吴安华
Owner 吴安华
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