Skip to main content

Advertisement

SpringerLink
Log in

Aberrant expression of BCL2A1-restricted minor histocompatibility antigens in melanoma cells: application for allogeneic transplantation

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

It has been shown that allogeneic hematopoietic stem cell transplantation (HSCT) can be one of the therapeutic options for patients with metastatic solid tumors, such as renal cancer. However, the development of relatively severe GVHD seems to be necessary to achieve tumor regression in the current setting. Thus, it is crucial to identify minor histocompatibility antigens (mHags) only expressed in tumor cells but not GVHD target organs. In this study, we examined whether three mHags: ACC-1 and ACC-2 encoded by BCL2A1, and HA-1 encoded by HMHA1, could serve as such targets for melanoma. Real-time PCR and immunohistochemical analysis revealed that the expression of both BCL2A1and HMHA1 in melanoma cell lines and primary melanoma cells was comparable to that of hematopoietic cells. Indeed, melanoma cell lines were efficiently lysed by cytotoxic T lymphocytes specific for ACC-1, ACC-2, and HA-1. Our data suggest that targeting mHags encoded not only by HMHA1, whose aberrant expression in solid tumors has been reported, but also BCL2A1 may bring about beneficial selective graft-versus-tumor effects in a population of melanoma patients for whom these mHags are applicable.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. den Haan JM, Meadows LM, Wang W, et al. The minor histocompatibility antigen HA-1: a diallelic gene with a single amino acid polymorphism. Science. 1998;279:1054–7.

    Article  Google Scholar 

  2. Kawase T, Akatsuka Y, Torikai H, et al. Alternative splicing due to an intronic SNP in HMSD generates a novel minor histocompatibility antigen. Blood. 2007;110:1055–63.

    Article  CAS  PubMed  Google Scholar 

  3. Bleakley M, Riddell SR. Molecules and mechanisms of the graft-versus-leukaemia effect. Nat Rev Cancer. 2004;4:371–80.

    Article  CAS  PubMed  Google Scholar 

  4. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17:2105–16.

    Article  CAS  PubMed  Google Scholar 

  5. McDermott DF. Update on the application of interleukin-2 in the treatment of renal cell carcinoma. Clin Cancer Res. 2007;13:716s–20s.

    Article  CAS  PubMed  Google Scholar 

  6. Ravaud A, Dilhuydy MS. Interferon alpha for the treatment of advanced renal cancer. Expert Opin Biol Ther. 2005;5:749–62.

    Article  CAS  PubMed  Google Scholar 

  7. Bishop MR, Fowler DH, Marchigiani D, et al. Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer. J Clin Oncol. 2004;22:3886–92.

    Article  PubMed  Google Scholar 

  8. Childs R, Chernoff A, Contentin N, et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000;343:750–8.

    Article  CAS  PubMed  Google Scholar 

  9. Klein CA, Wilke M, Pool J, et al. The hematopoietic system-specific minor histocompatibility antigen HA-1 shows aberrant expression in epithelial cancer cells. J Exp Med. 2002;196:359–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fujii N, Hiraki A, Ikeda K, et al. Expression of minor histocompatibility antigen, HA-1, in solid tumor cells. Transplantation. 2002;73:1137–41.

    Article  CAS  PubMed  Google Scholar 

  11. Miyazaki M, Akatsuka Y, Nishida T, et al. Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells. Clin Immunol. 2003;107:198–201.

    Article  CAS  PubMed  Google Scholar 

  12. Slager EH, Honders MW, van der Meijden ED, et al. Identification of the angiogenic endothelial-cell growth factor-1/thymidine phosphorylase as a potential target for immunotherapy of cancer. Blood. 2006;107:4954–60.

    Article  CAS  PubMed  Google Scholar 

  13. Akatsuka Y, Nishida T, Kondo E, et al. Identification of a polymorphic gene, BCL2A1, encoding two novel hematopoietic lineage-specific minor histocompatibility antigens. J Exp Med. 2003;197:1489–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Childs R, Srinivasan R. Advances in allogeneic stem cell transplantation: directing graft-versus-leukemia at solid tumors. Cancer J. 2002;8:2–11.

    Article  PubMed  Google Scholar 

  15. Su AI, Cooke MP, Ching KA, et al. Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci USA. 2002;99:4465–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kloosterboer FM, van Luxemburg-Heijs SA, van Soest RA, van Egmond HM, Willemze R, Falkenburg JH. Up-regulated expression in nonhematopoietic tissues of the BCL2A1-derived minor histocompatibility antigens in response to inflammatory cytokines: relevance for allogeneic immunotherapy of leukemia. Blood. 2005;106:3955–7.

    Article  CAS  PubMed  Google Scholar 

  17. Khammari A, Nguyen JM, Pandolfino MC, et al. Long-term follow-up of patients treated by adoptive transfer of melanoma tumor-infiltrating lymphocytes as adjuvant therapy for stage III melanoma. Cancer Immunol Immunother. 2007;56:1853–60.

    Article  PubMed  Google Scholar 

  18. Boon T, Coulie PG, Van den Eynde BJ, van der Bruggen P. Human T cell responses against melanoma. Annu Rev Immunol. 2006;24:175–208.

    Article  CAS  PubMed  Google Scholar 

  19. Machiels JP, van Baren N, Marchand M. Peptide-based cancer vaccines. Semin Oncol. 2002;29:494–502.

    Article  CAS  PubMed  Google Scholar 

  20. Yee C, Thompson JA, Byrd D, et al. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci USA. 2002;99:16168–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Dudley ME, Wunderlich JR, Robbins PF, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298:850–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dudley ME, Wunderlich JR, Yang JC, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005;23:2346–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kurokawa T, Fischer K, Bertz H, Hoegerle S, Finke J, Mackensen A. In vitro and in vivo characterization of graft-versus-tumor responses in melanoma patients after allogeneic peripheral blood stem cell transplantation. Int J Cancer. 2002;101:52–60.

    Article  CAS  PubMed  Google Scholar 

  24. Gottlieb DJ, Li YC, Lionello I, et al. Generation of tumour-specific cytotoxic T-cell clones from histocompatibility leucocyte antigen-identical siblings of patients with melanoma. Br J Cancer. 2006;95:181–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Akatsuka Y, Morishima Y, Kuzushima K, Kodera Y, Takahashi T. Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactions. Cancer Sci. 2007;98:1139–46.

    Article  CAS  PubMed  Google Scholar 

  26. Vlaykova T, Talve L, Hahka-Kemppinen M, et al. Immunohistochemically detectable bcl-2 expression in metastatic melanoma: association with survival and treatment response. Oncology. 2002;62:259–68.

    Article  CAS  PubMed  Google Scholar 

  27. Goulmy E, Schipper R, Pool J, et al. Mismatches of minor histocompatibility antigens between HLA-identical donors and recipients and the development of graft-versus-host disease after bone marrow transplantation. N Engl J Med. 1996;334:281–5.

    Article  CAS  PubMed  Google Scholar 

  28. Tseng LH, Lin MT, Hansen JA, et al. Correlation between disparity for the minor histocompatibility antigen HA-1 and the development of acute graft-versus-host disease after allogeneic marrow transplantation. Blood. 1999;94:2911–4.

    CAS  PubMed  Google Scholar 

  29. Murata M, Emi N, Hirabayashi N, et al. No significant association between HA-1 incompatibility and incidence of acute graft-versus-host disease after HLA-identical sibling bone marrow transplantation in Japanese patients. Int J Hematol. 2000;72:371–5.

    CAS  PubMed  Google Scholar 

  30. Nishida T, Akatsuka Y, Morishima Y, et al. Clinical relevance of a newly identified HLA-A24-restricted minor histocompatibility antigen epitope derived from BCL2A1, ACC-1, in patients receiving HLA genotypically matched unrelated bone marrow transplant. Br J Haematol. 2004;124:629–35.

    Article  CAS  PubMed  Google Scholar 

  31. Dickinson AM, Wang XN, Sviland L, et al. In situ dissection of the graft-versus-host activities of cytotoxic T cells specific for minor histocompatibility antigens. Nat Med. 2002;8:410–4.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Hiroki Torikai, Yoshiki Akatsuka, Kiyotaka Kuzushima & Toshitada Takahashi

  2. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Central Hospital, Nagoya, Japan

    Yasushi Yatabe

  3. Department of Hematology and Cell Therapy, Aichi Cancer Center Central Hospital, Nagoya, Japan

    Yasuo Morishima

  4. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Yoshihisa Kodera

Authors
  1. Hiroki Torikai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshiki Akatsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasushi Yatabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasuo Morishima
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshihisa Kodera
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kiyotaka Kuzushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Toshitada Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshiki Akatsuka.

About this article

Cite this article

Torikai, H., Akatsuka, Y., Yatabe, Y. et al. Aberrant expression of BCL2A1-restricted minor histocompatibility antigens in melanoma cells: application for allogeneic transplantation. Int J Hematol 87, 467–473 (2008). https://doi.org/10.1007/s12185-008-0076-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-008-0076-5

Keywords

Search

Navigation