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Recognition of neuroectodermal tumors by melanoma-specific cytotoxic T lymphocytes: evidence for antigen sharing by tumors derived from the neural crest

  • Original Articles
  • Melanoma, Neural crest, Ewing's Sarcoma, Tumorinfiltrating Lymphocyte
  • Published:
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Abstract

Melanomas from different patients have been shown to express shared tumor antigens, which can be recognized in the context of the appropriate MHC class 1 molecules by cytolytic T cells. To determine if T-cell-defined melanoma antigens are expressed on other tumors of neuroectodermal origin, four melanoma-specific cytotoxic T lymphocyte (CTL) cultures derived from tumor-infiltrating lymphocytes (TIL) were tested for lysis of a panel of 23 HLA-A2+ neuroectodermal tumor cell lines of various histologies, including retinoblastoma (1), neuroblastoma (8), neuroepithelioma (6), astrocytoma (2), neuroglioma (1), and Ewing's sarcoma (5). Low expression of MHC class I and/or ICAM-1 molecules was found on 22 of 23 neuroectodermal tumor lines, and could be enhanced by treatment with interferon γ (IFNγ). Following IFNγ treatment, three Ewing's sarcoma lines were lysed by at least one melanoma TIL culture, and levels of lysis were comparable to melanoma lysis by these TIL. Lysis could be inhibited by monoclonal antibodies directed against MHC class I molecules and against CD3, indicating specific immune recognition of tumor-associated antigens. None of the other neuroectodermal tumors tested were lysed by TIL, but they could be lysed by non-MHC-restricted lymphokine-activated killer cells. This demonstration of immunological cross-reactivity between melanomas and Ewing's sarcomas, two tumors of distinct histological types with a common embryonic origin, has implications for the developmental nature of these CTL-defined tumor antigens. It also raises the possibility that specific antitumor immunotherapies, such as vaccines, may be reactive against more than one form of cancer.

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References

  1. Anichini A, MacCalli C, Mortarini R, Salvi S, Mazzocchi A, Squarcina P, Herlyn M, Parmiani G (1993) Melanoma cells and normal melanocytes share antigens recognized by HLA-A2-restricted cytotoxic T cell clones from melanoma patients. J Exp Med 177: 989

    PubMed  Google Scholar 

  2. Brichard V, Van Pel A, Wolfel C, De Plaen E, Lethe B, Coulie P, Boon T (1993) The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 178: 489

    PubMed  Google Scholar 

  3. Cavazzana AO, Miser JS, Jefferson J, Triche TJ (1987) Experimental evidence for a neural origin of Ewing's sarcoma of bone. Am J Pathol 127: 507

    PubMed  Google Scholar 

  4. Cerundolo V, Alexander J, Anderson K, Lamb C, Cresswell P, McMichael A, Gotch F, Townsend A (1990) Presentation of viral antigen is controlled by a gene in the major histocompatibility complex. Nature 345: 449

    PubMed  Google Scholar 

  5. Crowley NJ, Darrow TL, Quinn-Aleen MA, Seigler HF (1991) MHC-restricted recognition of autologous melanoma by tumor specific cytotoxic T-cells: evidence for restriction by a dominant HLA-A allele. J Immunol 146: 1692

    PubMed  Google Scholar 

  6. Darrow DL, Slingluff CL, Siegler HF (1989) The role of HLA class I antigen in recognition of melanoma cells by tumor-specific cytotoxic T lymphocytes: evidence for shared tumor antigens. J Immunol 142: 3329

    PubMed  Google Scholar 

  7. Favrot MC, Combaret V, Goillot E, Tabone E, Bouffet E, Dolbeau D, Bouvier R, Coze C, Michon J, Philip T (1991) Expression of leucocyte adhesion molecules on 66 clinical neuroblastoma specimens. Int J Cancer 48: 502

    PubMed  Google Scholar 

  8. Hellstrom I, Garrigues HJ, Cabasco L, Mosley GH, Brown JP, Hellstrom KE (1983) Studies of a high molecular weight human melanoma-associated antigen. J Immunol 130: 1467

    PubMed  Google Scholar 

  9. Hom SS, Topalian SL, Simonis T, Mancini M, Rosenberg SA (1991) Common expression of melanoma tumor-associated antigens recognized by human tumor infiltrating lymphocytes: analysis by HLA restriction. J Immunother 10: 153

    PubMed  Google Scholar 

  10. Hom SS, Schwartzentruber DJ, Rosenberg SA, Topalian SL (1993) Specific release of cytokines by lymphocytes infiltrating human melanomas in response to shared melanoma antigens. J Immunother 13: 18

    PubMed  Google Scholar 

  11. Horowitz ME, Tsokos MG, Delaney TF (1992) Ewing's sarcoma. Cancer Clin 42: 300

    Google Scholar 

  12. Hosken NA, Bevan MJ (1990) Defective presentation of endogenous antigen by a cell line expressing class I molecules. Science 248: 367

    PubMed  Google Scholar 

  13. Kawakami Y, Zakut R, Topalian SL, Stotter H, Rosenberg SA (1992) Shared human melanoma antigens: Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. J Immunol 148: 638

    PubMed  Google Scholar 

  14. Main EK, Monos DS, Lampson LA (1988) IFN-treated neuroblastoma cell lines remain resistant to T cell-mediated allo-killing, and susceptible to non-MHC-restricted cytotoxicity. J Immunol 141: 2943

    PubMed  Google Scholar 

  15. Marincola FM, Shamamian P, Simonis TB, Abati A, Fetsch P, Restifo NP, Mulé JJ, Rosenberg SA (1993) Locus specific down-regulation of HLA class I in melanoma cell lines. Proc Am Assoc Cancer Res 34: 453

    Google Scholar 

  16. Naganuma H, Kiessling R, Patarroyo M, Hansson M, Handgretinger R, Gronberg A (1991) Increased susceptibility of IFN-γ treated neuroblastoma cells to lysis by lymphokine-activated killer cells: participation of ICAM-1 induction of target cells. Int J Cancer 47: 527

    PubMed  Google Scholar 

  17. O'Neil BH, Kawakami Y, Restifo NP, Bennink JR, Yewdell JW, Rosenberg SA (1993) Detection of shared MHC restricted human melanoma antigens following vaccinia virus mediated transduction of genes coding for HLA. J Immunol 151: 1410

    PubMed  Google Scholar 

  18. Restifo NP, Esquivel F, Kawakami Y, Yewdell JW, Mulé JJ, Rosenberg SA, Bennink JR (1993) Identification of human cancers deficient in antigen processing. J Exp Med 177: 265

    PubMed  Google Scholar 

  19. Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA, Simpson C, Carter C, Bock S, Schwartzentruber D, Wei JP, White DE (1988) Use of tumor infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma: preliminary report. N Engl J Med 819: 1676

    Google Scholar 

  20. Schwartzentruber DJ, Topalian SL, Mancini M, Rosenberg SA (1991) Specific release of GM-CSF, TNF-α and IFN-γ by human tumor infiltrating lymphocytes following autologous tumor stimulation. J Immunol 146: 3674

    PubMed  Google Scholar 

  21. Slingluff CL, Cox AL, Henderson RA, Hunt DF, Engelhard VH (1993) Recognition of human melanoma cells by HLA-A2.1-restricted cytotoxic T lymphocytes is mediated by at least six shared peptide epitopes. J Immunol 150: 2955

    PubMed  Google Scholar 

  22. Storkus WJ, Zeh HJ, Mauerer MJ, Salter RD, Lotze MT (1990) Identification of human melanoma peptides recognized by class I restricted tumor infiltrating T lymphocytes. J Immunol 151: 3719

    Google Scholar 

  23. Thiele CJ (1990) Pediatric peripheral neuroectodermal tumors, oncogenes, and differentiation. Cancer Invest 8: 629

    PubMed  Google Scholar 

  24. Topalian SL, Muul LM, Rosenberg SA (1987) Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. J Immunol Methods 102: 127

    PubMed  Google Scholar 

  25. Topalian SL, Solomon D, Avis FP, Chang AE, Freerksen DL, Linehan WM, Lotze MT, Robertson CN, Seipp CA, Simon P, Simpson CG, Rosenberg SA (1988) Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study. J Clin Oncol 6: 839

    PubMed  Google Scholar 

  26. Urmacher C, Cordon-Cardo C, Houghton AN (1989) Tissue distribution of GD3 ganglioside detected by mouse monoclonal antibody R24. Am J Dermatopathol 11: 577

    PubMed  Google Scholar 

  27. Van Den Eynde B, Hainaut P, Herin M, Knuth A, Lemoine C, Weynants P, Van Der Bruggen P, Fauchet R, Boon T (1989) Presence on a human melanoma of multiple antigens recognized by autologous CTL. Int J Cancer 41: 634

    Google Scholar 

  28. Van Der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van Den Eynde B, Knuth A, Boon T (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254: 1643

    PubMed  Google Scholar 

  29. Wolfel T, Klehmann E, Muller C, Schutt KH, Meyer Zum Buschefelde KH, Knuth A (1989) Lysis of human melanoma cells by autologous cytolytic T-cell clones: identification of human histocompatibility leukocyte antigen A2 as a restriction element for three different antigens. J Exp Med 170: 797

    PubMed  Google Scholar 

  30. Zachary AA, Teresi GA (eds) (1990) ASHI Laboratory Manual 2nd edn. American Society for Histocompatibility and Immunogenetics, New York, p 195

    Google Scholar 

  31. Zakut R, Topalian SL, Kawakami Y, Mancini M, Eliyahu S, Rosenberg SA (1993) Differential expression of MAGE-1,-2,-3 mRNA in transformed and normal human cell lines. Cancer Res 53: 5

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Surgery Branch, National Cancer Institute, Division of Cancer Treatment, National Institutes of Health, Building 10, Room 2B47, 20892, Bethesda, Maryland, USA

    Peter Shamamian, Marie Mancini, Yutaka Kawakami, Nicholas P. Restifo, Steven A. Rosenberg & Suzanne L. Topalian

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  1. Peter Shamamian
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  2. Marie Mancini
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  3. Yutaka Kawakami
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  4. Nicholas P. Restifo
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  5. Steven A. Rosenberg
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  6. Suzanne L. Topalian
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Shamamian, P., Mancini, M., Kawakami, Y. et al. Recognition of neuroectodermal tumors by melanoma-specific cytotoxic T lymphocytes: evidence for antigen sharing by tumors derived from the neural crest. Cancer Immunol Immunother 39, 73–83 (1994). https://doi.org/10.1007/BF01525312

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  • DOI: https://doi.org/10.1007/BF01525312

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