Simb16: Modeling induced immune system response against B16-melanoma

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. © 2011 Pappalardo et al.