TY - JOUR

T1 - Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies

AU - Argirion, Ilona

AU - Pfeiffer, Ruth M.

AU - Proietti, Carla

AU - Coghill, Anna E.

AU - Yu, Kelly J.

AU - Middeldorp, Jaap M.

AU - Sarathkumara, Yomani D.

AU - Hsu, Wan Lun

AU - Chien, Yin Chu

AU - Lou, Pei Jen

AU - Wang, Cheng Ping

AU - Rothman, Nathaniel

AU - Lan, Qing

AU - Chen, Chien Jen

AU - Mbulaiteye, Sam M.

AU - Jarrett, Ruth F.

AU - Glimelius, Ingrid

AU - Smedby, Karin E.

AU - Hjalgrim, Henrik

AU - Hildesheim, Allan

AU - Doolan, Denise L.

AU - Liu, Zhiwei

N1 - Funding Information: C.J. Chen reports grants from Ministry of Science and Technology during the conduct of the study. I. Glimelius reports other support from Takeda; and other support from Jansen Cilag outside the submitted work. No disclosures were reported by the other authors. Funding Information: A. Hildesheim was awarded funding from the Intramural Research Program of the NCI. This work was supported by the Intramural Research Program of NCI, USA. We are grateful to the study subjects without whom this work would not be possible. We thank Dr. Ellen T. Chang for comments on the manuscript. Publisher Copyright: ©2023 American Association for Cancer Research.

PY - 2023/5/1

Y1 - 2023/5/1

N2 - Background: Epstein–Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL). Methods: Anti-EBV IgG and IgA antibody responses targeting 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case–control studies investigating EBV-positive cHL, eBL, NPC, and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life-cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their association with each cancer type. In an additional analysis, we focused on the subset of 46 individual antibodies representing the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models. Results: IgA antibody responses targeting all EBV life-cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle; cHL with antibodies in the early lytic, late lytic and glycoprotein stages; and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types. Conclusions: Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis. Impact: Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer.

AB - Background: Epstein–Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL). Methods: Anti-EBV IgG and IgA antibody responses targeting 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case–control studies investigating EBV-positive cHL, eBL, NPC, and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life-cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their association with each cancer type. In an additional analysis, we focused on the subset of 46 individual antibodies representing the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models. Results: IgA antibody responses targeting all EBV life-cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle; cHL with antibodies in the early lytic, late lytic and glycoprotein stages; and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types. Conclusions: Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis. Impact: Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer.

U2 - 10.1158/1055-9965.EPI-22-0452

DO - 10.1158/1055-9965.EPI-22-0452

M3 - Journal article

C2 - 36788424

AN - SCOPUS:85159245724

VL - 32

SP - 687

EP - 696

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 5

ER -