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Cellular immunotherapy for malignant gliomas.

ABSTRACT: Cancer immunotherapy has made much progress in recent years. Clinical trials evaluating a variety of immunotherapeutic approaches are underway in patients with malignant gliomas. Thanks to recent advancements in cell engineering technologies, infusion of ex vivo prepared immune cells have emerged as promising strategies of cancer immunotherapy.Herein, the authors review recent and current studies using cellular immunotherapies for malignant gliomas. Specifically, they cover the following areas: a) cellular vaccine approaches using tumor cell-based or dendritic cell (DC)-based vaccines, and b) adoptive cell transfer (ACT) approaches, including lymphokine-activated killer (LAK) cells, ?? T cells, tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor (CAR)-T cells and T-cell receptor (TCR) transduced T cells.While some of the recent studies have shown promising results, the ultimate success of cellular immunotherapy in brain tumor patients would require improvements in the following areas: 1) feasibility in producing cellular therapeutics; 2) identification and characterization of targetable antigens given the paucity and heterogeneity of tumor specific antigens; 3) the development of strategies to promote effector T-cell trafficking; 4) overcoming local and systemic immune suppression, and 5) proper interpretation of imaging data for brain tumor patients receiving immunotherapy.

SUBMITTER: Lin Y

PROVIDER: S-EPMC5133460 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Cellular immunotherapy for malignant gliomas.

Lin Yi Y Okada Hideho H

Expert opinion on biological therapy 20160729 10

<h4>Introduction</h4>Cancer immunotherapy has made much progress in recent years. Clinical trials evaluating a variety of immunotherapeutic approaches are underway in patients with malignant gliomas. Thanks to recent advancements in cell engineering technologies, infusion of ex vivo prepared immune cells have emerged as promising strategies of cancer immunotherapy.<h4>Areas covered</h4>Herein, the authors review recent and current studies using cellular immunotherapies for malignant gliomas. Spe ...[more]

PMID: 27434205

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Project description:Despite a generally better prognosis than high-grade glioma (HGG), recurrence and malignant progression are the main causes for the poor prognosis and difficulties in the treatment of low-grade glioma (LGG). It is of great importance to learn about the risk factors and underlying mechanisms of LGG recurrence and progression. In this study, the transcriptome characteristics of four groups, namely, normal brain tissue and recurrent LGG (rLGG), normal brain tissue and secondary glioblastoma (sGBM), primary LGG (pLGG) and rLGG, and pLGG and sGBM, were compared using Chinese Glioma Genome Atlas (CGGA) and Genotype-Tissue Expression Project (GTEx) databases. In this study, 296 downregulated and 396 upregulated differentially expressed genes (DEGs) with high consensus were screened out. Univariate Cox regression analysis of data from The Cancer Genome Atlas (TCGA) yielded 86 prognostically relevant DEGs; a prognostic prediction model based on five key genes (HOXA1, KIF18A, FAM133A, HGF, and MN1) was established using the least absolute shrinkage and selection operator (LASSO) regression dimensionality reduction and multivariate Cox regression analysis. LGG was divided into high- and low-risk groups using this prediction model. Gene Set Enrichment Analysis (GSEA) revealed that signaling pathway differences in the high- and low-risk groups were mainly seen in tumor immune regulation and DNA damage-related cell cycle checkpoints. Furthermore, the infiltration of immune cells in the high- and low-risk groups was analyzed, which indicated a stronger infiltration of immune cells in the high-risk group than that in the low-risk group, suggesting that an immune microenvironment more conducive to tumor growth emerged due to the interaction between tumor and immune cells. The tumor mutational burden and tumor methylation burden in the high- and low-risk groups were also analyzed, which indicated higher gene mutation burden and lower DNA methylation level in the high-risk group, suggesting that with the accumulation of genomic mutations and epigenetic changes, tumor cells continued to evolve and led to the progression of LGG to HGG. Finally, the value of potential therapeutic targets for the five key genes was analyzed, and findings demonstrated that KIF18A was the gene most likely to be a potential therapeutic target. In conclusion, the prediction model based on these five key genes can better identify the high- and low-risk groups of LGG and lay a solid foundation for evaluating the risk of LGG recurrence and malignant progression.

Dataset Information

Cellular immunotherapy for malignant gliomas.

Publications

Cellular immunotherapy for malignant gliomas.

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