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HLA class I expression in metastatic melanoma correlates with tumor development during autologous vaccination

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Abstract

Our knowledge of the mechanisms underlying tumor-specific immune response and tumor escape has considerably increased. HLA class I antigen defects remain an important tumor escape mechanism since they influence the interactions between tumor cells and specific T and NK cells in the course of malignant disease. We have studied here HLA class I expression in six subcutaneous metastases obtained from a melanoma patient immunized with an autologous melanoma cell vaccine (M-VAX). We report in this paper that HLA class I antigen expression on these metastatic lesions strongly correlated with the course of the disease. The three metastases that were partially regressing at the time of their excision showed a strong HLA class I expression, whereas the progressing ones showed a very weak or negative staining with most of the anti-HLA class I mAbs used. Real-time quantitative PCR of the samples obtained from microdissected tumor tissue revealed a significant difference in the mRNA levels of HLA-ABC heavy chain and β2m between the two types of metastases, i.e., lower levels in progressing metastases and high levels in regressing ones, confirming the immunohistological findings. This is, to our knowledge, the first report where the clinical outcome of different HLA class I positive and negative melanoma metastases can be clearly correlated with the regression and progression of the disease, respectively.

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References

  1. Boon T, Coulie PG, Van den Eynde B (1997) Tumor antigens recognized by T cells. Immunol Today 18:267–268

    Article  CAS  PubMed  Google Scholar 

  2. Rosenberg SA (2001) Progress in human tumour immunology and immunotherapy. Nature 411:380–384

    Article  CAS  PubMed  Google Scholar 

  3. Coulie PG, van der Bruggen P (2003) T cell responses of vaccinated cancer patients. Curr Opin Immunol 15:131–137

    Article  CAS  PubMed  Google Scholar 

  4. Berd D (2004) M-VAX: an autologous, hapten-modified vaccine for human cancer. Expert Rev Vaccines 3:521–527

    Article  CAS  PubMed  Google Scholar 

  5. Marchand M, Brichard V, van Baren N, Coulie PG (2001) Biological and clinical developments in melanoma vaccines. Expert Opin Biol Ther 1:497–510

    Article  CAS  PubMed  Google Scholar 

  6. Rivoltini L, Canese P, Huber V, Iero M, Pilla L, Valenti R, Fais S, Lozupone F, Casati C, Castelli C, Parmiani G (2005) Escape strategies and reasons for failure in the interaction between tumour cells and the immune system: how can we tilt the balance towards immune-mediated cancer control? Expert Opin Biol Ther 5:463–476

    Article  CAS  PubMed  Google Scholar 

  7. Lonchay C, van der Bruggen P, Connerotte T, Hanagiri T, Coulie P, Colau D, Lucas S, Van Pel A, Thielemans K, van Baren N, Boon T (2004) Correlation between tumor regression and T cell responses in melanoma patients vaccinated with a MAGE antigen. Proc Natl Acad Sci USA 101(Supp12):14631–14638

    Article  CAS  PubMed  Google Scholar 

  8. Rosenberg SA, Dudley ME (2004) Cancer regression in patients with metastatic melanoma after the transfer of autologous antitumor 1ymphocytes. Proc Natl Acad Sci USA 101(Supp12):14639–14645

    Article  CAS  PubMed  Google Scholar 

  9. Liu M, Acres B, Balloul JM, Bizouarne N, Paul S, Slos P, Squiban P (2004) Gene-based vaccines and immunotherapeutics. Proc Natl Acad Sci USA 101(Supp12):14567–14571

    Article  CAS  PubMed  Google Scholar 

  10. Hersey P, Menzies SW, Coventry B, Nguyen T, Farrelly M, Collins S, Hirst D, Johnson H (2005) Phase I/II study of immunotherapy with T cell peptide epitopes in patients with stage IV me1anoma. Cancer Immunol Immunother 54:208–218

    Article  CAS  PubMed  Google Scholar 

  11. Lopez-Nevot MA, Garcia E, Romero C, Oliva MR, Serrano S, Garrido F (1988) Phenotypic and genetic analysis of HLA class I and HLA-DR antigen expression on human melanomas. Exp Clin Immunogenet 5:203–212

    CAS  PubMed  Google Scholar 

  12. Kageshita T, Ishihara T, Campoli M, Ferrone S (2005) Selective monomorphic and polymorphic HLA class I antigenic determinant loss in surgically removed melanoma lesions. Tissue Antigens 65:419–428

    Article  CAS  PubMed  Google Scholar 

  13. Garrido F, Ruiz-Cabello F, Cabrera T, Perez-Villar JJ, López-Botet M, Duggan-Keen M. Stern PL (1997) Implications for immunosurveillance of altered HLA class I phenotypes in human tumours. Immunol Today 18:89–95

    Article  CAS  PubMed  Google Scholar 

  14. Benitez R, Godelaine D, Lopez-Nevot MA, Brasseur F, Jimenez P, Marchand M, Oliva MR, van Baren N, Cabrera T, Andry G, Landry C, Ruiz-Cabello F, Boon T, Garrido F (1998) Mutations of the beta2-microglobulin gene result in a lack of HLA class I molecules on melanoma cells of two patients immunized with MAGE peptides. Tissue Antigens 52:520–529

    Article  CAS  PubMed  Google Scholar 

  15. Mendez R, Serrano A, Jager E, Maleno I, Ruiz-Cabello F, Knuth A, Garrido F (2001) Analysis of HLA class I expression in different metastases from two melanoma patients undergoing peptide immunotherapy. Tissue Antigens 57:508–519

    Article  CAS  PubMed  Google Scholar 

  16. Mendez R, Ruiz-Cabello F, Rodriguez T, Del Campo A, Paschen A, Schadendorf D, Garrido F (2006) Identification of different tumor escape mechanisms in several metastases from a melanoma patient undergoing immunotherapy. Cancer Immunol Immunother [Epub ahead of print] PMID: 16622680

  17. Maleno I, Cabrera CM, Cabrera T, López-Nevot MA, Collado A, Ferrón A, Garrido F (2004) Distribution of HLA class I phenotypes in colorectal carcinomas: high frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21. Immunogenetics 56:244–253

    Article  CAS  PubMed  Google Scholar 

  18. Pardoll D (2003) Does the immune system see tumors as foreign or self? Annu Rev Immunol 21:807–839

    Article  CAS  PubMed  Google Scholar 

  19. Khong HT, Restifo NP (2002) Natural selection of tumor variants in the generation of “tumor escape-phenotypes. Nat Immunol 3:999–1005

    Article  CAS  PubMed  Google Scholar 

  20. Tait BD (2000) HLA class I expression on human cancer cells. Hum Immunol 61:158–165

    Article  CAS  PubMed  Google Scholar 

  21. Algarra I, Garcia-Lora A, Cabrera T, Ruiz-Cabello F, Garrido F (2004) The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape. Cancer Immunol Immunother 10:904–910

    Google Scholar 

  22. Serrano A, Tanzarella S, Lionello I, Mendez R, Traversari C, Ruiz-Cabello F, Garrido F (2001) Rexpression of HLA class I antigens and restoration of antigen-specific CTL response in melanoma cells following 5-aza-2-deoxycytidine treatment. Int J Cancer 94:243–251

    Article  CAS  PubMed  Google Scholar 

  23. Paschen A, Mendez RM, Jimenez P, Sucker A, Ruiz-Cabello F, Song M, Garrido F, Schadendorf D (2003) Complete loss of HLA class I antigen expression on melanoma cells: a result of successive mutational events. Int J Cancer 103:759–767

    Article  CAS  PubMed  Google Scholar 

  24. Anichini A, Mortarini R, Nonaka D, Molla A, Vegetti C, Montaldi E, Wang X, Ferrone S (2006) Association of antigen-processing machinery and HLA antigen phenotype of melanoma cells with survival in American Joint Committee on Cancer stage III and IV melanoma patients. Cancer Res 66:6405–6411

    Article  CAS  PubMed  Google Scholar 

  25. Lehmann F, Marchand M, Hainaut P, Pouillart P, Sastre X, Ikeda H, Boon T, Coulie PG (1995) Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection. Eur J Immunol 25:340–347

    Article  CAS  PubMed  Google Scholar 

  26. Restifo NP, Marincola FM, Kawakami Y, Taubenberger J, Yannelli JR, Rosenberg SA (1996) Loss of functional beta 2-microglobulin in metastatic melanomas from five patients receiving immunotherapy. J Natl Cancer Inst 88:100–108

    Article  CAS  PubMed  Google Scholar 

  27. Garcia-Lora A, Algarra I, Gaforio JJ, Ruiz-Cabello F, Garrido F (2001) Immunoselection by T lymphocytes generates repeated MHC class I-deficient metastatic tumor variants. Int J Cancer 91:109–119

    Article  CAS  PubMed  Google Scholar 

  28. Griffioen M, Ouwerkerk IJ, Harten V, Schrier PI (2000) HLA-B locus-specific downregulation in human melanoma requires enhancer A as well as a sequence element located downstream of the transcription initiation site. Immunogenetics 52:121–128

    Article  CAS  PubMed  Google Scholar 

  29. Madjd Z, Spendlove I, Pinder SE, Ellis IO, Durrant LG (2005) Total loss of MHC class I is an independent indicator of good prognosis in breast cancer. Int J Cancer 117:248–255

    Article  CAS  PubMed  Google Scholar 

  30. Watson NF, Ramage JM, Madjd Z, Spendlove I, Ellis IO, Scholefield JH, Durrant LG (2006) Immunosurveillance is active in colorectal cancer as downregulation but not complete loss of MHC class I expression correlates with a poor prognosis. Int J Cancer 118:6–10

    Article  CAS  PubMed  Google Scholar 

  31. Rivoltini L, Carrabba M, Huber V, Castelli C, Novellino L, Dalerba P, Mortarini R, Arancia G, Anichini A, Fais S, Parmiani G (2002) Immunity to cancer: attack and escape in T lymphocyte–tumor cell interaction. Immunol Rev 188:97–113

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Ms. Ana Isabel Rodriguez for technical assistance. This work was partially supported by the Fondo de Investigaciones Sanitarias (FIS), Consejeria de Salud, Junta de Andalucia, by Plan Andaluz de Investigación (PAI) in Spain and by the European Network for the identification and validation of antigens and biomarkers in cancer and their application in clinical tumor immunology (ENACT, contract no. 503306).

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Authors and Affiliations

  1. Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Avd. Fuerzas Armadas 2, 18014, Granada, Spain

    Teresa Cabrera, Ester Lara, José M. Romero, Isabel Maleno, Francisco Ruiz-Cabello & Federico Garrido

  2. Departamento de Bioquímica, Biología Molecular 3 e Inmunología, Facultad de Medicina, Universidad de Granada, Granada, Spain

    Teresa Cabrera, Ester Lara, José M. Romero, Francisco Ruiz-Cabello & Federico Garrido

  3. Departamento de Genómica Estructural, Neocodex, Sevilla, Spain

    Luis M. Real

  4. Clinica Infanta Luisa, Sevilla, Spain

    Pedro Valero

  5. Departamento de Dermatología Médico-Quirúrgica y Venereología, Hospital Universitario “Virgen Macarena”, Universidad de Sevilla, Sevilla, Spain

    Francisco M. Camacho

Authors
  1. Teresa Cabrera
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  2. Ester Lara
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  3. José M. Romero
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  4. Isabel Maleno
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  5. Luis M. Real
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  6. Francisco Ruiz-Cabello
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  7. Pedro Valero
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  8. Francisco M. Camacho
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  9. Federico Garrido
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Correspondence to Federico Garrido.

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Cabrera, T., Lara, E., Romero, J.M. et al. HLA class I expression in metastatic melanoma correlates with tumor development during autologous vaccination. Cancer Immunol Immunother 56, 709–717 (2007). https://doi.org/10.1007/s00262-006-0226-7

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  • DOI: https://doi.org/10.1007/s00262-006-0226-7

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