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Peripheral blood test provides a practical method for glioma evaluation and prognosis prediction.

ABSTRACT: OBJECTIVE:To investigate the relationship between tumor characteristics and the preoperative counts of immune cells in peripheral blood test in glioma patients. METHODS:We included 260 WHO grades II-IV patients who had preoperative peripheral blood test result from Sanbo hospital as training set. The 66 patients from Tiantan hospital was obtained for validation. RNA sequencing data from CGGA and TCGA datasets were used to evaluate the features of neutrophil subtype and lymphocyte subtype in glioma. RESULTS:We revealed that the count of preoperative lymphocytes, eosinophils and neutrophils were associated with glioma grades. Neutrophil-to-lymphocyte ratio (NLR) <3.2 was associated with better prognosis, whereas increased NLR was strongly corresponding with a poor prognosis. Lymphocyte type glioma patients demonstrated a positive correlation with isocitrate dehydrogenase (IDH) mutation and lower grade. IDH mutant glioma contained a higher proportion of tumor-infiltrating lymphocytes than IDH wild-type glioma. The immune subtype (neutrophil subtype and lymphocyte subtype) was an independent prognostic factor in glioma. CONCLUSION:Our data demonstrated that NLR was an important prognostic factor in glioma. We classified that the immune subtype of glioma may contribute to a better understanding of disease pathogenesis and lead to the identification of new therapeutic targets for glioma patients.

SUBMITTER: Wang ZL

PROVIDER: S-EPMC6630006 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Peripheral blood test provides a practical method for glioma evaluation and prognosis prediction.

Wang Zhi-Liang ZL Zhang Chuan-Bao CB Liu Yu-Qing YQ Wang Zheng Z Jiang Tao T

CNS neuroscience & therapeutics 20190326 8

<h4>Objective</h4>To investigate the relationship between tumor characteristics and the preoperative counts of immune cells in peripheral blood test in glioma patients.<h4>Methods</h4>We included 260 WHO grades II-IV patients who had preoperative peripheral blood test result from Sanbo hospital as training set. The 66 patients from Tiantan hospital was obtained for validation. RNA sequencing data from CGGA and TCGA datasets were used to evaluate the features of neutrophil subtype and lymphocyte ...[more]

PMID: 30912613

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Project description:Background: Immune checkpoint inhibitors have been successfully used in a variety of tumors, however, the efficacy of immune checkpoint blockade therapy for patients with glioma is limited. In this study, we tried to clarify gene expression signatures related to the prognosis of gliomas and construct a signature to predict the survival of patients with gliomas. Methods: Calcium-related differential expressed genes (DEGs) between gliomas and normal brain tissues were comprehensively analyzed in two independent databases. Univariate, multivariate Cox regression analysis and proportional hazards model were used to identify the prognostic of calcium-related risk score signature. The CIBERSORT algorithm and association analysis were carried out to evaluate the relationship between calcium-related signature and characteristic clinical features, tumor-infiltrating immune cell signatures as well as immune checkpoint molecules in glioma. A nomogram model was developed for predicting the overall survival for patients with gliomas. Results: We found the intersection of 415 DEGs between gliomas and normal brain tissues, and identified that an eighteen calcium-related gene panel was significantly enriched in these DEGs. A calcium-related signature derived risk score was developed to divide patients into high- and low-risk groups. Low levels of calcium-related gene expression in high-risk score cases were accompanied with worse outcomes of patients. Calcium-related risk scores were significantly associated with characteristic clinical features, immune infiltrating signatures of tumor microenvironment, and exhausted T cell markers including programmed cell death 1 (PD-1), lymphocyte activating 3 (LAG3), and T cell membrane protein 3 (TIM-3), which contribute to an adverse therapeutic effect of immunotherapy. Calcium-related signature risk score was considered as an independent prognostic parameter to predict the of overall survival of patients with gliomas in nomogram model. Conclusion: Our study demonstrated that calcium signaling pathway is highly associated with immunosuppression of gliomas and overall survival of patients. Targeting the calcium signaling pathway might be a new strategy to reverse the immunosuppressive microenvironment of gliomas and improve the efficacy of glioma immunotherapy.

Project description:Our laboratory has recently demonstrated that natural killer (NK) cells are capable of eradicating orthotopically implanted mouse GL26 and rat CNS-1 malignant gliomas soon after intracranial engraftment if the cancer cells are rendered deficient in their expression of the ?-galactoside-binding lectin galectin-1 (gal-1). More recent work now shows that a population of Gr-1+/CD11b+ myeloid cells is critical to this effect. To better understand the mechanisms by which NK and myeloid cells cooperate to confer gal-1-deficient tumor rejection we have developed a comprehensive protocol for the isolation and analysis of glioma-infiltrating peripheral blood mononuclear cells (PBMC). The method is demonstrated here by comparing PBMC infiltration into the tumor microenvironment of gal-1-expressing GL26 gliomas with those rendered gal-1-deficient via shRNA knockdown. The protocol begins with a description of how to culture and prepare GL26 cells for inoculation into the syngeneic C57BL/6J mouse brain. It then explains the steps involved in the isolation and flow cytometric analysis of glioma-infiltrating PBMCs from the early brain tumor microenvironment. The method is adaptable to a number of in vivo experimental designs in which temporal data on immune infiltration into the brain is required. The method is sensitive and highly reproducible, as glioma-infiltrating PBMCs can be isolated from intracranial tumors as soon as 24 hr post-tumor engraftment with similar cell counts observed from time point matched tumors throughout independent experiments. A single experimentalist can perform the method from brain harvesting to flow cytometric analysis of glioma-infiltrating PBMCs in roughly 4-6 hr depending on the number of samples to be analyzed. Alternative glioma models and/or cell-specific detection antibodies may also be used at the experimentalists' discretion to assess the infiltration of several other immune cell types of interest without the need for alterations to the overall procedure.

Dataset Information

Peripheral blood test provides a practical method for glioma evaluation and prognosis prediction.

Publications

Peripheral blood test provides a practical method for glioma evaluation and prognosis prediction.

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