Multimodal immunogenomic biomarker analysis of tumors from pediatric patients enrolled to a phase 1-2 study of single-agent atezolizumab
|Study ID||Alternative Stable ID||Type|
We report herein an extensive exploratory biomarker analysis of refractory tumors taken from pediatric patients prior to receiving atezolizumab monotherapy in the phase 1-2 iMATRIX-atezolizumab trial (NCT02541604). A high percentage of CD8+ T cells and elevated protein levels of programmed cell death ligand 1 (PD-L1) were associated with progression-free survival (PFS). T-cell receptor (TCR) sequencing revealed that diverse infiltrating TCR repertoire at baseline was prognostic. We found no associations between panel-based tumor mutation burden (TMB) or specific genetic aberrations with PFS in this study. Through a pan-cancer gene co-expression network analysis, we developed a novel tumor-agnostic Pediatric Cytotoxicity and Antigen Presentation (PedCAP) signature that was associated with improved PFS in the iMATRIX-atezo study. Our study highlights features of immune response in pediatric cancers when treated with immune checkpoint inhibitors and provides a multi-biomarker pediatric immunogram framework to guide prospective clinical trials in pediatric cancers.
Study Datasets 8 datasets.
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Results of comprehensive immune deconvolution analysis through the TIMER2 web portal with algorithms specified in the publication.
Recurrently altered genes based on FoundationOne sequencing.
TCR-beta sequences, frequencies, and VDJ usage.
"Master" file of patient clinical characteristics and outcomes, samples, and the results of certain analyses, including immunohistochemistry.
Log2 gene expression count data from RNA sequencing.
TCR-beta specificity motifs based on GLIPH2.
Individual FASTQ files from RNA sequencing.
|Illumina HiSeq 2500||66|
Individual FASTQ files from TCR sequencing.
|Illumina NovaSeq 6000||45|
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