Immune evasion by murine melanoma mediated through CC chemokine receptor-10.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Murakami, T; Cardones, AR; Finkelstein, SE; Restifo, NP; Klaunberg, BA; Nestle, FO; Castillo, SS; Dennis, PA; Hwang, ST

Published Date

  • November 3, 2003

Published In

Volume / Issue

  • 198 / 9

Start / End Page

  • 1337 - 1347

PubMed ID

  • 14581607

Pubmed Central ID

  • 14581607

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.20030593


  • eng

Conference Location

  • United States