Tumor Immunology

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TAP expression reduces IL-10 expressing tumor infiltrating lymphocytes and restores immunosurveillance against melanoma

  1. Qian-Jin Zhang1,†,‡,
  2. Robyn P. Seipp1,2,3,‡,
  3. Susan S. Chen1,2,3,‡,
  4. Timothy Z. Vitalis1,
  5. Xiao-Lin Li1,†,
  6. Kyung-Bok Choi1,2,
  7. Andrew Jeffries1,2,
  8. Wilfred A. Jefferies1,2,3,4,5,*

Article first published online: 2 FEB 2007

DOI: 10.1002/ijc.22371

Issue

International Journal of Cancer

International Journal of Cancer

Volume 120, Issue 9, pages 1935–1941, 1 May 2007

Additional Information

How to Cite

Zhang, Q.-J., Seipp, R. P., Chen, S. S., Vitalis, T. Z., Li, X.-L., Choi, K.-B., Jeffries, A. and Jefferies, W. A. (2007), TAP expression reduces IL-10 expressing tumor infiltrating lymphocytes and restores immunosurveillance against melanoma. International Journal of Cancer, 120: 1935–1941. doi: 10.1002/ijc.22371

Author Information

  1. 1

    Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada

  2. 2

    Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada

  3. 3

    Department of Zoology, University of British Columbia, Vancouver, BC, Canada

  4. 4

    Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada

  5. 5

    Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada

  1. †

    Department of Cellular Biology and Anatomy, Gene Therapy Program, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA USA 71103

  1. ‡

    First three authors contributed equally to this work.

*Biomedical Research Center and the Michael Smith Laboratories, 2222 Health Sciences Mall, University of British Columbia, Vancouver, British Columbia, V6T 1Z3 Canada

Publication History

  1. Issue published online: 28 FEB 2007
  2. Article first published online: 2 FEB 2007
  3. Manuscript Accepted: 4 SEP 2006
  4. Manuscript Received: 28 SEP 2005

Funded by

  • CANVAC
  • CIHR
  • NCIC
  • GeneMax Pharmaceuticals

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Keywords:

  • TAP1;
  • MHC class I;
  • melanoma;
  • B16F10;
  • vaccinia;
  • mouse

Abstract

Many immune therapeutic strategies are under development for melanoma to treat metastatic disease and prevent disease reoccurrence. However, human melanoma cells are often deficient in antigen processing and this appears to play a role in their expansion and escape from immunosurveillance. For example, expression of the transporters associated with antigen processing (TAP1 and TAP2) is down-regulated in the mouse melanoma cell line B16F10. This results in a lack of tumor-associated antigen processing, low surface expression of MHC Class I molecules and low immunogenicity. We observe that restoration of TAP1 expression by transfection resurrects the processing and presentation of viral antigens, and the melanoma-associated antigen, TRP-2. Immunization with irradiated B16F10/rTAP1 transfected cells generates CTLs that are capable of killing B16F10/rTAP1 transfected targets and B16F10 targets deficient in TAP1. Furthermore, B16F10/rTAP1 transfectants grow at a significantly slower rate in mice than B16F10 cells. In an experimental model that closely recapitulates the clinical situation, treatment of B16F10 tumors in mice with a vaccinia virus vector expressing TAP1 also significantly decreases tumor growth in vivo. Furthermore, tumors treated with vaccinia TAP1 had significantly reduced numbers of immunosuppressive, CD3+/IL-10 positive, tumor infiltrating lymphocytes. Therefore, TAP1 expression restores both antigen presentation and immunogenicity in B16F10 melanoma cells and concomitantly reduces immunosuppressive IL-10 production at the local tumor site, thereby increasing immunosurveillance mechanisms against tumors. © 2007 Wiley-Liss, Inc.

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