Cel Tumors often engage the lymphatic system to invade and metastasize. The tumor-draining lymph node (dLN) may be an immune privileged site that protects the tumor from host immunity, and lymph flow draining tumors is often increased, enhancing communication between the tumor and the sentinel node. In addition to increasing transport of tumor antigens and regulatory cytokines to the lymph node, increased lymph flow in the tumor margin causes mechanical stress-induced changes in stromal cells that stiffen the matrix and alter the immune microenvironment of the tumor. In this proposed project, we will investigate the interplay between lymphatic drainage and flow-induced mechanotransduction in the tumor stroma that may synergize to promote tumor immune escape by appropriating lymphatic mechanisms of peripheral tolerance. We will address the hypothesis that lymphatic drainage and flow-induced mechanotransduction in the tumor stroma synergistically promote tumor immune escape by altering the immune microenvironment, and that targeting lymphatic drainage from the tumor may represent a new avenue for tumor immunotherapy. For the latter, we will develop strategies to limit or block lymphatic flow in the tumor microenvironment and characterize their ability to improve the efficacy of tumor immunotherapy by dampening local immunosuppression in the tumor stroma and tumor-draining lymph node (dLN). We will combine in vivo mouse models and intravital imaging with engineered in vitro microenvironments and nanoparticle-based targeting strategies in three broad aims designed to constitute several PhD and postdoctoral projects. Dziedzina nauki medical and health sciencesbasic medicineimmunologyimmunotherapy Program(-y) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Zaproszenie do składania wniosków ERC-2012-ADG_20120314 Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-AG - ERC Advanced Grant Instytucja przyjmująca ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Wkład UE € 2 217 581,66 Adres BATIMENT CE 3316 STATION 1 1015 Lausanne Szwajcaria Zobacz na mapie Region Schweiz/Suisse/Svizzera Région lémanique Vaud Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Caroline Vandevyver (Ms.) Kierownik naukowy Melody Ann Swartz (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Szwajcaria Wkład UE € 2 217 581,66 Adres BATIMENT CE 3316 STATION 1 1015 Lausanne Zobacz na mapie Region Schweiz/Suisse/Svizzera Région lémanique Vaud Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Caroline Vandevyver (Ms.) Kierownik naukowy Melody Ann Swartz (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych