Geographic EBV variants confound disease-specific variant interpretation and predict variable immune therapy responses.

Autor:	Briercheck EL; Division of Hematology and Oncology, University of Washington, Seattle, WA.; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA., Ravishankar S; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA., Ahmed EH; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, Columbus, OH., Carías Alvarado CC; Laboratorio de Investigación Biológica en Cáncer, Liga Nacional Contra el Cáncer & Instituto de Cancerología, Guatemala City, Guatemala., Barrios Menéndez JC; Laboratorio de Investigación Biológica en Cáncer, Liga Nacional Contra el Cáncer & Instituto de Cancerología, Guatemala City, Guatemala., Silva O; Department of Pathology, Stanford University School of Medicine, Stanford, CA.; Stanford University School of Medicine, Stanford, CA., Solórzano-Ortiz E; Laboratorio de Investigación Biológica en Cáncer, Liga Nacional Contra el Cáncer & Instituto de Cancerología, Guatemala City, Guatemala., Siliézar Tala MM; Laboratorio de Investigación Biológica en Cáncer, Liga Nacional Contra el Cáncer & Instituto de Cancerología, Guatemala City, Guatemala., Stevenson P; Division of Clinical Biostatistics, Fred Hutchinson Cancer Center, Seattle, WA., Xu Y; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA., Wohns AW; Stanford University School of Medicine, Stanford, CA., Enriquez-Vera D; Department of Pathology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru., Barrionuevo C; Department of Pathology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru., Yu SC; Department of Pathology at National Taiwan University Hospital, Taipei, Taiwan., Freud AG; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, Columbus, OH.; Department of Pathology Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, Columbus, OH., Oakes C; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, Columbus, OH.; Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH., Weigel C; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, Columbus, OH.; Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH., Weinstock DM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Klimaszewski HL; College of Medicine, The Ohio State University, Columbus, OH., Ngankeu A; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, Columbus, OH., Mutalima N; Epidemiology and Genetics Unit, Department of Health Sciences, University of York, York, United Kingdom., Samayoa-Reyes G; Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, CO., Newton R; Epidemiology and Genetics Unit, Department of Health Sciences, University of York, York, United Kingdom., Rochford R; Department of Immunology and Microbiology, University of Colorado, Anschutz Medical Campus, Aurora, CO., Valvert F; Laboratorio de Investigación Biológica en Cáncer, Liga Nacional Contra el Cáncer & Instituto de Cancerología, Guatemala City, Guatemala., Natkunam Y; Department of Pathology, Stanford University School of Medicine, Stanford, CA.; Stanford University School of Medicine, Stanford, CA., Shustov A; Division of Hematology and Oncology, University of Washington, Seattle, WA.; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA., Baiocchi RA; Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, Columbus, OH.; Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH., Warren EH; Division of Hematology and Oncology, University of Washington, Seattle, WA.; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Jul 23; Vol. 8 (14), pp. 3731-3744.
DOI:	10.1182/bloodadvances.2023012461
Abstrakt:	Abstract: Epstein-Barr virus (EBV) is a potent carcinogen linked to hematologic and solid malignancies and causes significant global morbidity and mortality. Therapy using allogeneic EBV-specific lymphocytes shows promise in certain populations, but the impact of EBV genome variation on these strategies remains unexplored. To address this, we sequenced 217 EBV genomes, including hematologic malignancies from Guatemala, Peru, Malawi, and Taiwan, and analyzed them alongside 1307 publicly available EBV genomes from cancer, nonmalignant diseases, and healthy individuals across Africa, Asia, Europe, North America, and South America. These included, to our knowledge, the first natural killer (NK)/T-cell lymphoma (NKTCL) EBV genomes reported outside of East Asia. Our findings indicate that previously proposed EBV genome variants specific to certain cancer types are more closely tied to geographic origin than to cancer histology. This included variants previously reported to be specific to NKTCL but were prevalent in EBV genomes from other cancer types and healthy individuals in East Asia. After controlling for geographic region, we did identify multiple NKTCL-specific variants associated with a 7.8-fold to 21.9-fold increased risk. We also observed frequent variations in EBV genomes that affected peptide sequences previously reported to bind common major histocompatibility complex alleles. Finally, we found several nonsynonymous variants spanning the coding sequences of current vaccine targets BALF4, BKRF2, BLLF1, BXLF2, BZLF1, and BZLF2. These results highlight the need to consider geographic variation in EBV genomes when devising strategies for exploiting adaptive immune responses against EBV-related cancers, ensuring greater global effectiveness and equity in prevention and treatment. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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