Dataset Information

Transcriptional immunogenomic analysis reveals distinct immunological clusters in paediatric nervous system tumours.

ABSTRACT:

Background

Cancer immunotherapies including immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR) T-cell therapy have shown variable response rates in paediatric patients highlighting the need to establish robust biomarkers for patient selection. While the tumour microenvironment in adults has been widely studied to delineate determinants of immune response, the immune composition of paediatric solid tumours remains relatively uncharacterized calling for investigations to identify potential immune biomarkers.

Methods

To inform immunotherapy approaches in paediatric cancers with embryonal origin, we performed an immunogenomic analysis of RNA-seq data from 925 treatment-naïve paediatric nervous system tumours (pedNST) spanning 12 cancer types from three publicly available data sets.

Results

Within pedNST, we uncovered four broad immune clusters: Paediatric Inflamed (10%), Myeloid Predominant (30%), Immune Neutral (43%) and Immune Desert (17%). We validated these clusters using immunohistochemistry, methylation immune inference and segmentation analysis of tissue images. We report shared biology of these immune clusters within and across cancer types, and characterization of specific immune cell frequencies as well as T- and B-cell repertoires. We found no associations between immune infiltration levels and tumour mutational burden, although molecular cancer entities were enriched within specific immune clusters.

Conclusions

Given the heterogeneity of immune infiltration within pedNST, our findings suggest personalized immunogenomic profiling is needed to guide selection of immunotherapeutic strategies.

SUBMITTER: Nabbi A

PROVIDER: S-EPMC10486055 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Transcriptional immunogenomic analysis reveals distinct immunological clusters in paediatric nervous system tumours.

Nabbi Arash A Beck Pengbo P Delaidelli Alberto A Oldridge Derek A DA Sudhaman Sumedha S Zhu Kelsey K Yang S Y Cindy SYC Mulder David T DT Bruce Jeffrey P JP Paulson Joseph N JN Raman Pichai P Zhu Yuankun Y Resnick Adam C AC Sorensen Poul H PH Sill Martin M Brabetz Sebastian S Lambo Sander S Malkin David D Johann Pascal D PD Kool Marcel M Jones David T W DTW Pfister Stefan M SM Jäger Natalie N Pugh Trevor J TJ

Genome medicine 20230907 1

<h4>Background</h4>Cancer immunotherapies including immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR) T-cell therapy have shown variable response rates in paediatric patients highlighting the need to establish robust biomarkers for patient selection. While the tumour microenvironment in adults has been widely studied to delineate determinants of immune response, the immune composition of paediatric solid tumours remains relatively uncharacterized calling for investigations to iden ...[more]

PMID: 37679810

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Dataset Information

Transcriptional immunogenomic analysis reveals distinct immunological clusters in paediatric nervous system tumours.

Background

Methods

Results

Conclusions

Publications

Transcriptional immunogenomic analysis reveals distinct immunological clusters in paediatric nervous system tumours.

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