Multimodal immunogenomic biomarker analysis of tumors from pediatric patients enrolled to a phase 1-2 study of single-agent atezolizumab.

Autor: Nabbi A; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Danesh A; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Espin-Garcia O; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.; Dalla Lana School of Public Health and Department of Statistical Sciences, University of Toronto, Toronto, Ontario, Canada., Pedersen S; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Wellum J; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Fu LH; Clinical Biomarker Operations, Product Development Oncology, Genentech, South San Francisco, CA, USA., Paulson JN; Department of Biostatistics, Product Development, Genentech, South San Francisco, CA, USA., Geoerger B; Gustave Roussy Cancer Centre, Department of Pediatric and Adolescent Oncology, INSERM U1015, Université Paris-Saclay, Villejuif, France., Marshall LV; The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London, UK., Trippett T; Memorial Sloan Kettering Cancer Center, New York, NY, USA., Rossato G; Product Development Clinical Oncology, F. Hoffmann-La Roche, Basel, Switzerland., Pugh TJ; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. trevor.pugh@utoronto.ca.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. trevor.pugh@utoronto.ca.; Ontario Institute for Cancer Research, Toronto, Ontario, Canada. trevor.pugh@utoronto.ca., Hutchinson KE; Oncology Biomarker Development, Genentech, South San Francisco, CA, USA. hutchinson.katherine@gene.com.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2023 Apr; Vol. 4 (4), pp. 502-515. Date of Electronic Publication: 2023 Apr 10.
DOI: 10.1038/s43018-023-00534-x
Abstrakt: 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).)
Databáze: MEDLINE
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