crosstalk between medulloblastoma cells and endothelium triggers a strong chemotactic signal recruiting t lymphocytes to the tumor microenvironment成神经管细胞瘤细胞之间的串扰和内皮触发强烈趋化信号招募t淋巴细胞肿瘤微环境.pdfVIP

Crosstalk between Medulloblastoma Cells and Endothelium Triggers a Strong Chemotactic Signal Recruiting T Lymphocytes to the Tumor Microenvironment Vita S. Salsman1,2,3, Kevin K. H. Chow1,2,3, Donald R. Shaffer1,2,3, Huseyin Kadikoy1,2,3, Xiao-Nan Li2,3, 1,2,3 2,3 1,2,3,4 1,2,3,4 4 Claudia Gerken , Laszlo Perlaky , Leonid S. Metelitsa , Xiuhua Gao , Meena Bhattacharjee , Karen Hirschi1,4, Helen E. Heslop1,2,3,5, Stephen Gottschalk1,2,3,4, Nabil Ahmed1,2,3* 1 Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, United States of America, 2 Texas Children’s Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America, 3 Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America, 4 Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America, 5 Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America 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