simb16 modeling induced immune system response against b16-melanomasimb16建模对b16-melanoma诱导的免疫系统反应.pdfVIP

SimB16: Modeling Induced Immune System Response against B16-Melanoma 1. 2. 1 2 2 Francesco Pappalardo , Ivan Martinez Forero , Marzio Pennisi , Asis Palazon , Ignacio Melero *, Santo Motta1 1 University of Catania, Catania, Italy, 2 CIMA and CUN University of Navarra Pamplona, Pamplona, Spain Abstract Immunological therapy of progressive tumors requires not only activation and expansion of tumor specific cytotoxic T lymphocytes (CTLs), but also an efficient effector phase including migration of CTLs in the tumor tissue followed by conjugation and killing of target cells. We report the application of an agent-based model to recapitulate both the effect of a specific immunotherapy strategy against B16-melanoma in mice and the tumor progression in a generic tissue section. A comparison of the in silico results with the in vivo experiments shows excellent agreement. We therefore use the model to predict a critical role for CD137 expression on tumor vessel endothelium for successful therapy and other mechanistic aspects. Experimental results are fully compatible with the model predictions. The biologically oriented in silico model derived in this work will be used to predict treatment failure or success in other pre-clinical conditions eventually leading new promising in vivo experiments. Citation: Pappalardo F, Forero IM, Pennisi M, Palazon A, Melero I, et al. (2011) SimB16: Modeling Induced Immune System Response against B16-Melanoma. PLoS ONE 6(10): e26523. doi:10.1371/journal.pone.0026523 Editor: Vladimir Brusic, Dana-Farber Cancer Institute, United States of America Received August 4, 2011; Accepted September 28, 2011; Published October