Human melanoma cells frequently express CC chemokine receptor (CCR)10, a receptor whose ligand (CCL27) is constitutively produced by keratinocytes. Compared with B16 murine melanoma, cells rendered more immunogenic via overexpression of luciferase, B16 cells that overexpressed both luciferase and CCR10 resisted host immune responses and readily formed tumors. In vitro, exposure of tumor cells to CCL27 led to rapid activation of Akt, resistance to cell death induced by melanoma antigen-specific cytotoxic T cells, and phosphatidylinositol-3-kinase (PI3K)–dependent protection from apoptosis induced by Fas cross-linking. In vivo, cutaneous injection of neutralizing antibodies to endogenous CCL27 blocked growth of CCR10-expressing melanoma cells. We propose that CCR10 engagement by locally produced CCL27 allows melanoma cells to escape host immune antitumor killing mechanisms (possibly through activation of PI3K/Akt), thereby providing a means for tumor progression.
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3 November 2003
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October 27 2003
Immune Evasion by Murine Melanoma Mediated through CC Chemokine Receptor-10
Takashi Murakami,
Takashi Murakami
1Dermatology, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
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Adela R. Cardones,
Adela R. Cardones
1Dermatology, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
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Steven E. Finkelstein,
Steven E. Finkelstein
2Surgery, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
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Nicholas P. Restifo,
Nicholas P. Restifo
2Surgery, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
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Brenda A. Klaunberg,
Brenda A. Klaunberg
5Department of Dermatology, University of Zürich Hospital, CH-8091 Zürich, Switzerland
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Frank O. Nestle,
Frank O. Nestle
4National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892
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S. Sianna Castillo,
S. Sianna Castillo
3Cancer Therapeutics Branches, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
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Phillip A. Dennis,
Phillip A. Dennis
3Cancer Therapeutics Branches, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
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Sam T. Hwang
Sam T. Hwang
1Dermatology, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
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Takashi Murakami
1Dermatology, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
Adela R. Cardones
1Dermatology, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
Steven E. Finkelstein
2Surgery, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
Nicholas P. Restifo
2Surgery, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
Brenda A. Klaunberg
5Department of Dermatology, University of Zürich Hospital, CH-8091 Zürich, Switzerland
Frank O. Nestle
4National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892
S. Sianna Castillo
3Cancer Therapeutics Branches, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
Phillip A. Dennis
3Cancer Therapeutics Branches, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
Sam T. Hwang
1Dermatology, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
Address correspondence to Sam T. Hwang, Bldg. 10/Rm. 12N246, 10 Center Dr., Bethesda, MD 20892-1908. Phone: (301) 496-8724; Fax: (301) 496-5370; email: [email protected]
Abbreviations used in this paper: CCR, CC chemokine receptor; CXCR, CXC chemokine receptor; IHC, immunohistochemistry; p-Akt, phospho-Akt; PI3K, phosphatidylinositol-3-kinase.
The online version of this article includes supplemental material.
Received:
April 11 2003
Revision Received:
August 08 2003
Accepted:
September 12 2003
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 198 (9): 1337–1347.
Article history
Received:
April 11 2003
Revision Received:
August 08 2003
Accepted:
September 12 2003
Citation
Takashi Murakami, Adela R. Cardones, Steven E. Finkelstein, Nicholas P. Restifo, Brenda A. Klaunberg, Frank O. Nestle, S. Sianna Castillo, Phillip A. Dennis, Sam T. Hwang; Immune Evasion by Murine Melanoma Mediated through CC Chemokine Receptor-10 . J Exp Med 3 November 2003; 198 (9): 1337–1347. doi: https://doi.org/10.1084/jem.20030593
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