Children with endemic Burkitt lymphoma are deficient in EBNA1-specific IFN-gamma T cell responses
Department of Quantitative Health Sciences; Department of Pediatrics
Medical Subject Headings
Burkitt Lymphoma; Child; *Endemic Diseases; Enzyme-Linked Immunosorbent Assay; Epstein-Barr Virus Infections; Epstein-Barr Virus Nuclear Antigens; Herpesvirus 4, Human; Humans; Immunoglobulin G; Interferon-gamma; Kenya; T-Lymphocytes; Viral Load
Biostatistics | Epidemiology | Health Services Research | Immunology and Infectious Disease | Pediatrics
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.
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Citation: Int J Cancer. 2009 Apr 1;124(7):1721-6. Link to article on publisher's site
Moormann, Ann M.; Heller, Kevin N.; Chelimo, Kiprotich; Embury, Paula E.; Ploutz-Snyder, Robert; Otieno, Juliana A.; Oduor, Margaret; Munz, Christian; and Rochford, Rosemary A., "Children with endemic Burkitt lymphoma are deficient in EBNA1-specific IFN-gamma T cell responses" (2008). Quantitative Health Sciences Publications and Presentations. 407.