Landscape of tumor-infiltrating T cell repertoire of pediatric brain tumors

Email Principal Investigator
Ongoing
Data
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Gary Kohanbash

UPMC Children's Hospital of Pittsburgh
Pittsburgh, PA, USA

CBTN Data Used

Backer

Brain Tumor Funders' Collaborative

St Baldrick's Foundation

About this

Project

Cellular immunity mediated by T-cells is responsible for the detection and neutralization of pathogenic threats. T-cell receptors (TCRs) are highly specialized extracellular receptors that are essential to T-cell specificity and can characterize the T-cell immune status in patients, and normal individuals. TCRs are heterodimers composed of distinct subunits (α- and β-), and versatility of the TCR population in an individual is shaped by the somatic rearrangement of variable (V), diversity (D), and joining (J) gene segments together with insertions and deletions. Majority of TCR variation occurs within the complementarity-determining region 3 (CDR3), and the sequence of CDR3 is widely used to classify TCR variants. The extraordinary diversity of TCRs is a major bottleneck to determine the antigen specificity of a given T cell.

The incidence of pediatric brain tumors ranges between 1-5 cases every 100,000 persons and is the leading cause of cancer death in children (Landi, Thompson, & Ashley, 2018). Understanding the immune environment of pediatric brain tumors is a requisite for immune-based therapies. Immune repertoire deep sequencing at the genomic DNA or cDNA level is limited by the availability of tumor tissue for sequencing, and less power to detect TCR repertoires from a subset of data. Transcriptome sequencing has become a routine in basic as well as clinical studies, and could additionally be used for profiling of TCR repertoires at no additional cost. Several groups have reported methods that extract TCR repertoire from bulk or single cell data from different types of cancer (Bolotin et al., 2015; Li et al., 2016, 2017, 2018).

Ask The

Scientists

Ask the scientists

What are the goals of this project?

Here, we aim to characterize the TCR repertoire of the pediatric brain tumor microenvironment using bulk RNA-Seq data from Children’s Brain Tumor Network (CBTN). Moreover, a systematic analysis of tumor-associated TCR signatures is of great importance for the identification of the driving antigen, and help uncover potential targets for immunotherapy. Lastly, the large amount of samples present in the CBTTC will allow used for comparison of T-cells CDR3 regions and gene signatures within bulk RNAseq, to our ongoing collection of single-cell RNAseq from these tumors.

What is the impact of this project?

Such a computational meta-analysis of bulk RNA samples from pediatric brain tumor will provide the key to unlock the potential of the T-cell receptor repertoire, and to provide powerful biomarkers.

Specimen Data

The Children's Brain Tumor Network contributed to this project by providing access to the Pediatric Brain Tumor Atlas.

Explore the data in these informatics portals

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Meet The

Team

Other collaborators:

Alberto Broniscer (CHP), Udai Kammula (UPMC)