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Int J Cancer. 2009 Apr 1;124(7):1721-6. doi: 10.1002/ijc.24014.

Children with endemic Burkitt lymphoma are deficient in EBNA1-specific IFN-gamma T cell responses.

Author information

1
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH.

Abstract

Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in equatorial Africa and is linked to Epstein-Barr virus (EBV) and Plasmodium falciparum coinfections early in life. Epstein-Barr nuclear antigen 1 (EBNA1) is the sole viral latent antigen expressed in BL tumors. Loss of EBNA1-specific immune surveillance could allow eBL emergence. Therefore, EBNA1-specific T cell responses were analyzed by IFN-gamma ELISPOT in Kenyan children with eBL and compared to healthy children with divergent malaria exposure. Significantly fewer children with eBL, 16% (7/44) had EBNA1-specific IFN-gamma responses in contrast to healthy children living in a malaria holoendemic area or in an area with sporadic malaria transmission, 67% (40/60) and 72% (43/60) responders, respectively (p < 0.003). Children with eBL maintained IgG(1) dominated antibody responses to EBNA1 similar to healthy children suggesting a selective loss of IFN-gamma secreting EBNA1-specific T cells in the presence of intact humoral immunity. CD8(+) T cell responses to EBV lytic and latent antigens not expressed in the tumors were similarly robust in eBL patients compared to healthy children. In addition, CD4(+) T cell responses to a malaria protein, merozoite surface protein 1, were present in lymphoma patients. This study demonstrates a selective loss of EBNA1-specific T cell responses in children with eBL and suggests a potential immunotherapeutic target for this EBV-associated lymphoma.

PMID:
19089927
PMCID:
PMC2708320
DOI:
10.1002/ijc.24014
[Indexed for MEDLINE]
Free PMC Article

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