Medical Oncology and Tumor Pharmacotherapy

, Volume 4, Issue 3–4, pp 177–186 | Cite as

Viruses and cancer risks: Outgrowth of Epstein-Barr virus-positive Burkitt's lymphoma in the immune host

  • A. B. Rickinson
  • C. D. Gregory
  • L. S. Young
Viruses and Cancer Risks


This work examines ways in which Epstein-Barr (EB) virus-positive Burkitt's lymphoma (BL) cells achieve outgrowthin vivo in the face of prevailing EB virus-specific cytotoxic T-cell surveillance. Earlier work has shown that some, but not all, BL cell linesin vitro are insensitive to virus-specific T-cell cytolysis and the present study identifies two mechanisms whereby the tumour cells might evade detection. First, BL-cell lines which stably retain the original tumour cell phenotype on serial passagein vitro show very low expression of two cell adhesion-related molecules, LFA-1 and ICAM 1, and are negative for a third such molecule, LFA-3; these molecules are thought to play a crucial role in the non antigen-dependent phase of effector: target cell conjugation which precedes antigen-specific recognition and target cell lysis. Secondly, those same BL cell lines display an unusually restricted pattern of EB virus latent gene expression with at least two potentially important target proteins for the T-cell response, namely EBNA 2 and LMP, not detectably expressed.

Key words

EB virus Burkitt's lymphoma Cell phenotype Viral proteins T-cell recognition 


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  1. 1.
    Sixbey J W, Nedrud J G, Raab-Traub N, Hanes R A, Pagano J S: Epstein-Barr virus replication in oropharyngeal epithelial cells.New Engl J Med 310, 1225 (1984).PubMedGoogle Scholar
  2. 2.
    Wolf H, Haus M, Wilmer E: Persistence of Epstein-Barr virus in the parotid gland.J Virol 51, 795 (1984).PubMedGoogle Scholar
  3. 3.
    Yao Q Y, Rickinson A B, Epstein M A: A reexamination of the Epstein-Barr virus carrier state in healthy seropositive individuals.Int J Cancer 35, 35 (1985).PubMedCrossRefGoogle Scholar
  4. 4.
    Nemerow G R, Mold C, Schwend V K, Tollefson V, Cooper N R: Identification of gp350 as the viral glycoprotein mediating attachment of Epstein-Barr virus (EBV) to the EBV/C3d receptor of B cells: sequence homology of gp350 and C3 complement fragment C3d.J Virol 61, 1416 (1987).PubMedGoogle Scholar
  5. 5.
    Dambaugh T, Hennessy K, Fennewald S, Kieff E: The virus genome and its expression in latent infection, in Epstein M A, Achong B G (eds):The Epstein-Barr Virus: Recent Advances, pp. 13–45. London, William Heinemann (1986).Google Scholar
  6. 6.
    Hennessy K, Wang F, Woodland Bushman E, Kieff E: Definitive identification of, a member of the Epstein-Barr virus nuclear protein 3 family.Proc Natn Acad Sci U.S.A. 83, 5693 (1986).CrossRefGoogle Scholar
  7. 7.
    Sample J, Hummel M, Braun D, Birkenbach M, Kieff, E: Nucleotide sequences of mRNAs encoding Epstein-Barr virus nuclear proteins: a probable transcriptional initiation site.Proc Natn Acad Sci U.S.A. 83, 5096 (1986).CrossRefGoogle Scholar
  8. 8.
    Rickinson A B, Moss D J, Wallace L E, Rowe M, Misko I S, Epstein M A, Pope J H: Long-term T-cell-mediated immunity to Epstein-Barr virus.Cancer Res 41 4216 (1981).PubMedGoogle Scholar
  9. 9.
    Lenoir G M: Role of the virus, chromosomal translocations and cellular oncogenes in the aetiology of Burkitt's lymphoma, in Epstein M A, Achong B G (eds),The Epstein-Barr Virus: Recent Advances, pp. 183–205. London, William Heinemann (1986).Google Scholar
  10. 10.
    Cleary M L, Dorfman R F, Sklar J: Failure in immunological control of the virus infection: post-transplant lymphomas, in Epstein M A, Achong B G (eds):The Epstein-Barr Virus: Recent Advances, pp. 163–181. London, William Heinemann (1986).Google Scholar
  11. 11.
    Crawford D H, Edwards J M B, Sweny P, Hoffbrand A V, Janossy G: Studies on long-term T-cell-mediated immunity to Epstein-Barr virus in immunosuppressed renal allograft recipients.Int J Cancer 28, 705 (1981).PubMedCrossRefGoogle Scholar
  12. 12.
    Rooney C M, Rickinson A B, Moss D J, Lenoir G M, Epstein M A: Cell-mediated immunosurveillance mechanisms and the pathogenesis of Burkitt's lymphoma, in Lenoir G M, O'Conor G T O, Olweny C L M (eds):Burkitt's Lymphoma: A Human Cancer Model, vol. 60, pp. 249–264, Lyon, IARC Scientific Publications (1985).Google Scholar
  13. 13.
    Lenoir G M, Vuillaume M, Bonnardel C: Use of lymphomatous and lymphoblastoid cell lines in the study of Burkitt's lymphoma, in, Lenoir G M, O'Conor G, Olweny C L M (eds):Burkitt Lymphoma: A Human Cancer Model, vol. 60, pp. 309–318. Lyon, IARC Scientific Publications (1985).Google Scholar
  14. 14.
    Rooney C M, Gregory C D, Rowe M, Finerty S, Edwards C, Rupani H, Rickinson A B: Endemic Burkitt's lymphoma: phenotypic analysis of Burkitt's lymphoma biopsy cells and of the derived tumour cell lines.J Natn Cancer Inst 77, 681 (1986).Google Scholar
  15. 15.
    Rowe M, Rooney C M, Rickinson A B, Lenoir G M, Rupani H, Moss D J, Stein H, Epstein M A: Distinctions between endemic and sporadic forms of Epstein-Barr virus-positive Burkitt's lymphoma.Int J Cancer 35, 435 (1985).PubMedCrossRefGoogle Scholar
  16. 16.
    Wiels J, Fellous M, Tursz T: Monoclonal antibody against a Burkitt lymphoma-associated antigen.Proc Natn Acad Sci U.S.A. 78, 6485 (1981).CrossRefGoogle Scholar
  17. 17.
    Ritz J, Pesando J M, Notis-McConarty J, Lazarus H, schlossman S F: A monoclonal antibody to human acute lymphoblastic leukeaemia antigen.Nature (Lond)283, 583 (1980).PubMedCrossRefGoogle Scholar
  18. 18.
    Stein H, Gerdes J, Schwab U, Lemke H, Diehl V, Mason D, Bartels H, Ziegler A: Evidence for the detection of the normal counterpart of Hodgkin and Sternberg-Reed cells.Haemat Oncol 1, 21 (1983).CrossRefGoogle Scholar
  19. 19.
    Rowe M, Hildreth J E K, Rickinson A B, Epstein M A: Monoclonal antibodies to Epstein-Barr virusinduced, transformation-associated cell surface antigens: binding patterns and effect upon virus-specific T-cell cytotoxicity.Int J Cancer 29, 373 (1982).PubMedCrossRefGoogle Scholar
  20. 20.
    Schwab U, Stein H, Gerdes J, Lemke H, Kirchner H, Schaadt M, Diehl V: Production of a monoclonal antibody specific for Hodgkin and Sternberg-Reed cells of Hodgkin's disease and a subset of normal lymphoid cells.Nature (Lond),299, 65 (1982).CrossRefGoogle Scholar
  21. 21.
    Hildreth J E, Gotch F M, Hildreth P D, McMichael A J: A human lymphocyte-associated antigen involved in cell-mediated lympholysis.Eur J Immun 13, 202 (1983).CrossRefGoogle Scholar
  22. 22.
    Rothlein R, Dustin M L, Marlin S D, Springer T A: A human intercellular adhesion molecule (ICAM 1) distinct from LFA-1.J Immun 137, 1270 (1986).PubMedGoogle Scholar
  23. 23.
    Sanchez-Madrid F, Krensky A M, Ware C F, Robbins E, Strominger J L, Burakoff S J, Springer T A: Three distinct antigens associated with human T lymphocyte-mediated cytolysis: LFA-1, LFA-2 and LFA-3.Proc Natn Acad Sci U.S.A. 79, 7489 (1982).CrossRefGoogle Scholar
  24. 24.
    Barnstable C J, Bodmer W F, Brown G, Galfre G, Milstein C, Williams A F, Ziegler A: Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens—new tools for genetic analysis.Cell 14, 9 (1978).PubMedCrossRefGoogle Scholar
  25. 25.
    Rooney C M, Edwards C F, Lenoir G M, Rupani H, Rickinson A B: Differential activation of cytotoxic responses by Burkitt's lymphoma (BL)-cell lines: relationship to the BL-cell surface phenotype.Cell Immun 102, 99 (1986).CrossRefGoogle Scholar
  26. 26.
    Wallace L E, Rowe M, Gaston J S H, Rickinson A B, Epstein M A: Cytotoxic T cell recognition of Epstein-Barr infected B cells III. Establishment of HLA-restricted cytotoxic T cell lines using interleukin 2.Eur J Immun 12, 1012 (1982).CrossRefGoogle Scholar
  27. 27.
    Rowe D T, Rowe M, Evans G I, Wallace L E, Farrell P J, Rickinson A B: Restricted expression of EBV latent genes and T-lymphocyte detected membrane antigen in Burkitt's lymphoma cells.EMBO J 5, 2599 (1986).PubMedGoogle Scholar
  28. 28.
    Rowe M, Evans H S, Young L S, Hennessy K, Kieff E, Rickinson A B: Monoclonal antibodies to the latent membrane protein of Epstein-Barr virus reveal heterogeneity of the protein and inducible expression in virus-transformed cells.J Gen Virol 68, 1575 (1987).PubMedCrossRefGoogle Scholar
  29. 29.
    Rooney C M, Rickinson A B, Moss D J, Lenoir G M, Epstein M A: Paired Epstein-Barr virus-carrying lymphoma and lymphoblastoid cell lines from Burkitt's lymphoma patients: comparative sensitivity to non-specific and to allo-specific cytotoxic responsesin vitro.Int J Cancer 34, 339 (1984).PubMedCrossRefGoogle Scholar
  30. 30.
    Rooney C M, Rowe M, Wallace L E, Rickinson A B: Epstein-Barr virus-positive Burkitt's lymphoma cells not recognised by virus-specific T-cell surveillance.Nature 317, 629 (1985).PubMedCrossRefGoogle Scholar
  31. 31.
    Rothlein R, Springer T A: The requirement for lymphocyte function-associated antigen 1 in homotypic leucocyte adheseion stimulated by phorbol ester.J Exp Med 163, 1132 (1986).PubMedCrossRefGoogle Scholar
  32. 32.
    Shaw S, Luce G E G, Quinones R, Gress R E, Springer T A, Sanders M E: Two antigen-independent adhesion pathways used by human cytotoxic T cell clones.Nature 323, 262 (1986).PubMedCrossRefGoogle Scholar
  33. 33.
    Rowe M, Rowe D T, Gregory C D, Young L S, Farrell P J, Rupani H, Rickinson A B: Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt's lymphoma cells.EMBO J 6, 2743 (1987).PubMedGoogle Scholar
  34. 34.
    Dambaugh T, Hennessy K, Chamnankit L, Kieff E: U2 region of Epstein-Barr virus DNA may encode Epstein-Barr nuclear antigen 2.Proc Natn Acad Sci U.S.A. 81, 7632 (1984).CrossRefGoogle Scholar
  35. 35.
    Nilsson K, Klein G: Phenotypic and cytogenetic characteristics of human B lymphoid cell lines and their relevance for the etiology of Burkitt's lymphoma.Adv Cancer Res 37, 319 (1982).PubMedCrossRefGoogle Scholar
  36. 36.
    Gregory C D, Tursz T, Edwards C F, Tetaud C, Talbot M, Caillou B, Rickinson A B, Lipinski M: Identification of a subset of normal B cells with a Burkitt's lymphoma (BL)-like phenotype.J Immun 139, 313 (1987).PubMedGoogle Scholar
  37. 37.
    Lombardi L, Newcomb E W, Dalla-Favera R: Pathogenesis of Burkitt Lymphoma: expression of an activatedc-myc oncogene causes the tumorigenic conversion of EBV-infected human B lymphoblasts.Cell 49, 161 (1987).PubMedCrossRefGoogle Scholar

Copyright information

© Pergamon Press Ltd. 1987

Authors and Affiliations

  • A. B. Rickinson
    • 1
  • C. D. Gregory
    • 1
  • L. S. Young
    • 1
  1. 1.Department of Cancer StudiesUniversity of BirminghamBirminghamU.K.

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