The Neo-Open Reading Frame Peptides That Comprise the Tumor Framome Are a Rich Source of Neoantigens for Cancer Immunotherapy.

Autor:	Martin MV; CureVac Netherlands B.V., Amsterdam, the Netherlands., Aguilar-Rosas S; CureVac Netherlands B.V., Amsterdam, the Netherlands., Franke K; CureVac Netherlands B.V., Amsterdam, the Netherlands., Pieterse M; CureVac Netherlands B.V., Amsterdam, the Netherlands., Langelaar JV; CureVac Netherlands B.V., Amsterdam, the Netherlands., Schreurs R; CureVac Netherlands B.V., Amsterdam, the Netherlands., Bijlsma MF; Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands., Besselink MG; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands.; Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands., Koster J; Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Amsterdam, the Netherlands., Timens W; Department of Pathology and Medical Biology, University of Groningen, University, Medical Center Groningen, the Netherlands., Khasraw M; Duke University Medical Center, Duke University, Durham, North Carolina., Ashley DM; Preston Robert Tisch Brain Tumor Center, Department of Neurosurgery, Duke University, Durham, North Carolina., Keir ST; Duke University Medical Center, Duke University, Durham, North Carolina., Ottensmeier CH; Liverpool Head and Neck Centre, Institute of Systems, Molecular and Integrative Biology, University of Liverpool and Clatterbridge Cancer Center NHS Foundation Trust, Liverpool, UK., King EV; Department of Otorhinolaryngology, Head and Neck Surgery, Poole Hospital, Poole, UK., Verheij J; Amsterdam UMC, location University of Amsterdam, Department of Pathology, Amsterdam, the Netherlands., Waasdorp C; Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Amsterdam, the Netherlands., Valk PJM; Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands., Engels SAG; The Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Oostenbach E; The Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., van Dinter JT; The Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Hofman DA; The Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Mok JY; Sanquin Reagents, Sanquin, Amsterdam, the Netherlands., van Esch WJE; Sanquin Reagents, Sanquin, Amsterdam, the Netherlands., Wilmink H; Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands.; Amsterdam UMC, location University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands., Monkhorst K; Netherlands Cancer Institute, Amsterdam, the Netherlands., Verheul HMW; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Poel D; Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the, Netherlands., Hiltermann TJN; Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, the Netherlands., Kempen LCLTV; Department of Pathology and Medical Biology, University of Groningen, University, Medical Center Groningen, the Netherlands.; University of Antwerp, Antwerp University Hospital, Edegem, Belgium., Groen HJM; Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, the Netherlands., Aerts JGJV; Erasmus Medical Center, Pulmonary Medicine, Rotterdam, the Netherlands., Heesch SV; The Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Löwenberg B; CureVac Netherlands B.V., Amsterdam, the Netherlands., Plasterk R; CureVac Netherlands B.V., Amsterdam, the Netherlands., Kloosterman WP; CureVac Netherlands B.V., Amsterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	Cancer immunology research [Cancer Immunol Res] 2024 Jun 04; Vol. 12 (6), pp. 759-778.
DOI:	10.1158/2326-6066.CIR-23-0158
Abstrakt:	Identification of immunogenic cancer neoantigens as targets for therapy is challenging. Here, we integrate the whole-genome and long-read transcript sequencing of cancers to identify the collection of neo-open reading frame peptides (NOP) expressed in tumors. We termed this collection of NOPs the tumor framome. NOPs represent tumor-specific peptides that are different from wild-type proteins and may be strongly immunogenic. We describe a class of hidden NOPs that derive from structural genomic variants involving an upstream protein coding gene driving expression and translation of noncoding regions of the genome downstream of a rearrangement breakpoint, i.e., where no gene annotation or evidence for transcription exists. The entire collection of NOPs represents a vast number of possible neoantigens particularly in tumors with many structural genomic variants and a low number of missense mutations. We show that NOPs are immunogenic and epitopes derived from NOPs can bind to MHC class I molecules. Finally, we provide evidence for the presence of memory T cells specific for hidden NOPs in peripheral blood from a patient with lung cancer. This work highlights NOPs as a major source of possible neoantigens for personalized cancer immunotherapy and provides a rationale for analyzing the complete cancer genome and transcriptome as a basis for the detection of NOPs. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu