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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Burkitt Lymphoma / epidemiology*
  • Burkitt Lymphoma / immunology*
  • Burkitt Lymphoma / virology
  • Child
  • Endemic Diseases*
  • Enzyme-Linked Immunosorbent Assay
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / immunology
  • Epstein-Barr Virus Nuclear Antigens / immunology*
  • Herpesvirus 4, Human / immunology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Interferon-gamma / immunology*
  • Kenya
  • T-Lymphocytes / immunology*
  • Viral Load


  • Epstein-Barr Virus Nuclear Antigens
  • Immunoglobulin G
  • Interferon-gamma
  • EBV-encoded nuclear antigen 1