1. Crosstalk between medulloblastoma cells and endothelium triggers a strong chemotactic signal recruiting T lymphocytes to the tumor microenvironment
- Author
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Meenakshi B. Bhattacharjee, Xiao-Nan Li, Claudia Gerken, Laszlo Perlaky, Kevin Chow, Vita S. Salsman, Xiuhua Gao, Karen K. Hirschi, Nabil Ahmed, Helen E. Heslop, Stephen Gottschalk, Leonid S. Metelitsa, Donald R. Shaffer, and Huseyin Kadikoy
- Subjects
Male ,Chemokine ,T-Lymphocytes ,Tumor Physiology ,Cancer Treatment ,lcsh:Medicine ,Pediatrics ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Lymphocytes, Tumor-Infiltrating ,Basic Cancer Research ,Tumor Microenvironment ,Animals ,Humans ,Cerebellar Neoplasms ,lcsh:Science ,Chemokine CCL5 ,Macrophage Migration-Inhibitory Factors ,Neurological Tumors ,030304 developmental biology ,Immune Evasion ,0303 health sciences ,Tumor microenvironment ,Multidisciplinary ,biology ,Chemotaxis ,lcsh:R ,Brain ,Endothelial Cells ,Cancers and Neoplasms ,T lymphocyte ,3. Good health ,Cell biology ,CCL20 ,Oncology ,Pediatric Oncology ,030220 oncology & carcinogenesis ,Cancer cell ,biology.protein ,Medicine ,Macrophage migration inhibitory factor ,lcsh:Q ,Immunotherapy ,Medulloblastoma ,Signal Transduction ,Research Article - 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.
- Published
- 2011