title: Crosstalk between medulloblastoma cells and endothelium triggers a strong chemotactic signal recruiting T lymphocytes to the tumor microenvironment.
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.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Vita S
authors.initials: VS
authors.lastname: Salsman
authors.forename: Kevin K H
authors.initials: KK
authors.lastname: Chow
authors.forename: Donald R
authors.initials: DR
authors.lastname: Shaffer
authors.forename: Huseyin
authors.initials: H
authors.lastname: Kadikoy
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Li
authors.forename: Claudia
authors.initials: C
authors.lastname: Gerken
authors.forename: Laszlo
authors.initials: L
authors.lastname: Perlaky
authors.forename: Leonid S
authors.initials: LS
authors.lastname: Metelitsa
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Gao
authors.forename: Meena
authors.initials: M
authors.lastname: Bhattacharjee
authors.forename: Karen
authors.initials: K
authors.lastname: Hirschi
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
authors.forename: Stephen
authors.initials: S
authors.lastname: Gottschalk
authors.forename: Nabil
authors.initials: N
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002528:Cerebellar Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018946:Chemokine CCL5 / Q000378:metabolism; D002633:Chemotaxis; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D008297:Male; D008527:Medulloblastoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D018946:Chemokine CCL5; D008263:Macrophage Migration-Inhibitory Factors