Dataset Information

Preferential Infiltration of Unique V?9J?2-V?2 T Cells Into Glioblastoma Multiforme.

ABSTRACT: Glioblastoma multiforme (GBM) is clinically highly aggressive as a result of evolutionary dynamics induced by cross-talk between cancer cells and a heterogeneous group of immune cells in tumor microenvironment. The brain harbors limited numbers of immune cells with few lymphocytes and macrophages; thus, innate-like lymphocytes, such as ?? T cells, have important roles in antitumor immunity. Here, we characterized GBM-infiltrating ?? T cells, which may have roles in regulating the GBM tumor microenvironment and cancer cell gene expression. V(D)J repertoires of tumor-infiltrating and blood-circulating ?? T cells from four patients were analyzed by next-generation sequencing-based T-cell receptor (TCR) sequencing in addition to mutation and immune profiles in four GBM cases. In all tumor tissues, abundant innate and effector/memory lymphocytes were detected, accompanied by large numbers of tumor-associated macrophages and closely located tumor-infiltrating ?? T cells, which appear to have anti-tumor activity. The immune-related gene expression analysis using the TCGA database showed that the signature gene expression extent of ?? T cells were more associated with those of cytotoxic T and Th1 cells and M1 macrophages than those of Th2 cells and M2 macrophages. Although the most abundant ?? T cells were V?9V?2 T cells in both tumor tissues and blood, the repertoire of intratumoral V?9V?2 T cells was distinct from that of peripheral blood V?9V?2 T cells and was dominated by V?9J?2 sequences, not by canonical V?9J?P sequences that are mostly commonly found in blood ?? T cells. Collectively, unique GBM-specific TCR clonotypes were identified by comparing TCR repertoires of peripheral blood and intra-tumoral ?? T cells. These findings will be helpful for the elucidation of tumor-specific antigens and development of anticancer immunotherapies using tumor-infiltrating ?? T cells.

SUBMITTER: Lee M

PROVIDER: S-EPMC6440384 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Preferential Infiltration of Unique Vγ9Jγ2-Vδ2 T Cells Into Glioblastoma Multiforme.

Lee Mijeong M Park Chanho C Woo Jeongmin J Kim Jinho J Kho Inseong I Nam Do-Hyun DH Park Woong-Yang WY Kim Yeon-Soo YS Kong Doo-Sik DS Lee Hye Won HW Kim Tae Jin TJ

Frontiers in immunology 20190322

Glioblastoma multiforme (GBM) is clinically highly aggressive as a result of evolutionary dynamics induced by cross-talk between cancer cells and a heterogeneous group of immune cells in tumor microenvironment. The brain harbors limited numbers of immune cells with few lymphocytes and macrophages; thus, innate-like lymphocytes, such as γδ T cells, have important roles in antitumor immunity. Here, we characterized GBM-infiltrating γδ T cells, which may have roles in regulating the GBM tumor micro ...[more]

PMID: 30967876

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Project description:Glioma is the most common primary brain tumor and glioblastoma multiforme (GBM) is the most malignant brain glioma with the worst prognosis. T cell immune regulator 1 (TCIRG1) constitutes the V0a3 subunit of vacuolar ATPase (V-ATPase), and the function of V-ATPase in malignant tumors, such as breast cancer, melanoma and hepatocellular carcinoma, has been reported. However, the effect of the TCIRG1 subunit on GBM remains to be fully elucidated. mRNA levels of TCIRG1 in different cancer types and the corresponding normal tissues were extracted from the Oncomine and Tumor Immune Estimation Resource (TIMER) databases. The Gene Expression Omnibus (access number: GSE16011), the Chinese Glioma Genome Atlas and The Cancer Genome Atlas were used to investigate the mRNA level of TCIRG1 in glioma. Protein level validation in glioma was performed using western blotting. The Database for Annotation, Visualization and Integrated Discovery was used to analyze Gene Ontology (GO) categories for genes correlated with TCIRG1 in GBM. Protein-protein interaction (PPI) networks and module analyses were performed using Cytoscape software and the MCODE plugin. The correlation between tumor immune cell infiltration and TCIRG1 expression was explored using the TIMER database. Additionally, the correlation between TCIRG1 and the gene signature of immune infiltration was explored through TIMER and Gene Expression Profiling Interactive Analysis. External validation of TCIRG1 expression according to immune signatures in GBM was performed using the GSE16011 dataset with the GlioVis online tool. It was found that TCIRG1 expression was increased in GBM and numerous malignant tumors and may serve as a biomarker of the mesenchymal subtype of GBM. GO category analysis of positively correlated genes revealed that TCIRG1 was correlated with the immune response in GBM. PPI network and module analyses also supported the potential function of TCIRG1 in the local immune response. The expression of TCIRG1 was associated with various immune markers. It was therefore speculated that TCIRG1 is associated with glioma malignancy and may be a marker of unfavorable prognosis in patients with GBM, and it could be regarded as a prognostic biomarker and an indicator of immune infiltration in GBM.

Dataset Information

Preferential Infiltration of Unique V?9J?2-V?2 T Cells Into Glioblastoma Multiforme.

Publications

Preferential Infiltration of Unique Vγ9Jγ2-Vδ2 T Cells Into Glioblastoma Multiforme.

Similar Datasets

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