Immune Evasion by Murine Melanoma Mediated through CC Chemokine Receptor-10

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1337-1347
Number of pages11
JournalJournal of Experimental Medicine
Volume198
Issue number9
DOIs
StatePublished - Nov 3 2003
Externally publishedYes

Fingerprint

CCR10 Receptors
Immune Evasion
Melanoma
Phosphatidylinositol 3-Kinase
Luciferases
Melanoma-Specific Antigens
Neoplasms
Experimental Melanomas
Neutralizing Antibodies
Keratinocytes
Cell Death
Apoptosis
Ligands
T-Lymphocytes
Skin
Injections
Growth

Keywords

  • Cancer
  • Cell signaling
  • Chemokine receptor
  • Metastasis

ASJC Scopus subject areas

  • Immunology

Cite this

Murakami, T., Cardones, A. R., Finkelstein, S. E., Restifo, N. P., Klaunberg, B. A., Nestle, F. O., ... Hwang, S. T. (2003). Immune Evasion by Murine Melanoma Mediated through CC Chemokine Receptor-10. Journal of Experimental Medicine, 198(9), 1337-1347. https://doi.org/10.1084/jem.20030593

Immune Evasion by Murine Melanoma Mediated through CC Chemokine Receptor-10. / Murakami, Takashi; Cardones, Adela R.; Finkelstein, Steven E.; Restifo, Nicholas P.; Klaunberg, Brenda A.; Nestle, Frank O.; Castillo, S. Sianna; Dennis, Phillip A.; Hwang, Sam T.

In: Journal of Experimental Medicine, Vol. 198, No. 9, 03.11.2003, p. 1337-1347.

Research output: Contribution to journalArticle

Murakami, T, Cardones, AR, Finkelstein, SE, Restifo, NP, Klaunberg, BA, Nestle, FO, Castillo, SS, Dennis, PA & Hwang, ST 2003, 'Immune Evasion by Murine Melanoma Mediated through CC Chemokine Receptor-10', Journal of Experimental Medicine, vol. 198, no. 9, pp. 1337-1347. https://doi.org/10.1084/jem.20030593
Murakami T, Cardones AR, Finkelstein SE, Restifo NP, Klaunberg BA, Nestle FO et al. Immune Evasion by Murine Melanoma Mediated through CC Chemokine Receptor-10. Journal of Experimental Medicine. 2003 Nov 3;198(9):1337-1347. https://doi.org/10.1084/jem.20030593
Murakami, Takashi ; Cardones, Adela R. ; Finkelstein, Steven E. ; Restifo, Nicholas P. ; Klaunberg, Brenda A. ; Nestle, Frank O. ; Castillo, S. Sianna ; Dennis, Phillip A. ; Hwang, Sam T. / Immune Evasion by Murine Melanoma Mediated through CC Chemokine Receptor-10. In: Journal of Experimental Medicine. 2003 ; Vol. 198, No. 9. pp. 1337-1347.
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