Crosstalk between medulloblastoma cells and endothelium triggers a strong chemotactic signal recruiting t lymphocytes to the tumor microenvironment

Vita S. Salsman, Kevin K.H. Chow, Donald R. Shaffer, Huseyin Kadikoy, Xiao Nan Li, Claudia Gerken, Laszlo Perlaky, Leonid S. Metelitsa, Xiuhua Gao, Meena Bhattacharjee, Karen Hirschi, Helen E. Heslop, Stephen Gottschalk, Nabil Ahmed*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Cancer cells can live and grow if they succeed in creating a favorable niche that often includes elements from the immune system. While T lymphocytes play an important role in the host response to tumor growth, the mechanism of their trafficking to the tumor remains poorly understood. We show here that T lymphocytes consistently infiltrate the primary brain cancer, medulloblastoma. We demonstrate, both in vitro and in vivo, that these T lymphocytes are attracted to tumor deposits only after the tumor cells have interacted with tumor vascular endothelium. Macrophage Migration Inhibitory Factor (MIF)" is the key chemokine molecule secreted by tumor cells which induces the tumor vascular endothelial cells to secrete the potent T lymphocyte attractant "Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES)." This in turn creates a chemotactic gradient for RANTES-receptor bearing T lymphocytes. Manipulation of this pathway could have important therapeutic implications.

Original languageEnglish (US)
Article numbere20267
JournalPloS one
Volume6
Issue number5
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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