Multimodal immunogenomic biomarker analysis of tumors from pediatric patients enrolled to a phase 1-2 study of single-agent atezolizumab Journal Article
| Authors: | Nabbi, A.; Danesh, A.; Espin-Garcia, O.; Pedersen, S.; Wellum, J.; Fu, L. H.; Paulson, J. N.; Geoerger, B.; Marshall, L. V.; Trippett, T.; Rossato, G.; Pugh, T. J.; Hutchinson, K. E. |
| Article Title: | Multimodal immunogenomic biomarker analysis of tumors from pediatric patients enrolled to a phase 1-2 study of single-agent atezolizumab |
| Abstract: | We report herein an exploratory biomarker analysis of refractory tumors collected from pediatric patients before atezolizumab therapy (iMATRIX-atezolizumab, NCT02541604). Elevated levels of CD8+ T cells and PD-L1 were associated with progression-free survival and a diverse baseline infiltrating T-cell receptor repertoire was prognostic. Differential gene expression analysis revealed elevated expression of CALCA (preprocalcitonin) and CCDC183 (highly expressed in testes) in patients who experienced clinical activity, suggesting that tumor neoantigens from these genes may contribute to immune response. In patients who experienced partial response or stable disease, elevated Igα2 expression correlated with T- and B-cell infiltration, suggesting that tertiary lymphoid structures existed in these patients’ tumors. Consensus gene co-expression network analysis identified core cellular pathways that may play a role in antitumor immunity. Our study uncovers features associated with response to immune-checkpoint inhibition in pediatric patients with cancer and provides biological and translational insights to guide prospective biomarker profiling in future clinical trials. © 2023, The Author(s). |
| Keywords: | immunohistochemistry; osteosarcoma; adult; cancer survival; child; human tissue; protein expression; major clinical study; overall survival; genetics; clinical trial; nuclear magnetic resonance imaging; dna replication; protein localization; neoplasm; neoplasms; cd8+ t lymphocyte; tumor associated leukocyte; cd8-positive t-lymphocytes; biomarkers; biological marker; quality control; ipilimumab; cancer immunotherapy; melanoma; progression free survival; phase 2 clinical trial; cell infiltration; prevalence; cell differentiation; antineoplastic activity; cytotoxicity; renal cell carcinoma; b lymphocyte; monoclonal antibody; t lymphocyte receptor; regulatory t lymphocyte; immune response; mismatch repair; immunogenicity; cd4+ t lymphocyte; tumor immunity; phase 1 clinical trial; spindle cell sarcoma; cytotoxic t lymphocyte antigen 4; rna processing; transcriptome; rna metabolism; rna extraction; antibody titer; nephroblastoma; alveolar soft part sarcoma; programmed death 1 ligand 1; tumor microenvironment; nucleic acid base substitution; multimodal imaging; antibodies, monoclonal, humanized; high throughput sequencing; nivolumab; myosin light chain; humans; human; male; female; article; tertiary lymphoid structure; pembrolizumab; differential expression analysis; atezolizumab; chemiluminescence immunoassay; pediatric patient; protein fingerprinting; whole transcriptome sequencing; refractory tumor |
| Journal Title: | Nature Cancer |
| Volume: | 4 |
| Issue: | 4 |
| ISSN: | 2662-1347 |
| Publisher: | Nature Research |
| Date Published: | 2023-04-01 |
| Start Page: | 502 |
| End Page: | 515 |
| Language: | English |
| DOI: | 10.1038/s43018-023-00534-x |
| PUBMED: | 37038005 |
| PROVIDER: | scopus |
| PMCID: | PMC10132976 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 31 May 2023 -- Source: Scopus |
