17. June 2019

Bettina Weigelin

Intravital multiphoton and higher harmonic generation microscopy for visualizing tumor invasion and immunotherapy

Eberhard Karls University of Tübingen / Tübingen, Germany

Cell migration is an adaptive process based on cell-intrinsic properties to migrate individually or collectively, and their adaptation to encountered tissue structures acting as barrier or providing guidance. Whereas molecular and physical mechanisms of cancer and immune cell migration are well-studied in 3D in vitro models, their topographic relevance, classification and validation towards interstitial tissue organization in vivoremain incomplete. Using intravital multiphoton microscopy and higher harmonic generation we mapped tissue spaces and geometry in live tumors in relation to tumor cell invasion routes and immune cell infiltration during immunotherapy. Using in vivo immunohistochemistry, fluorescent tracer injections and correlated electron microscopy we characterized the molecular and ultrastructural microtopography of preexisting tumor invasion-promoting tissue niches. Dynamic time-lapse imaging of immune cell infiltration further revealed guidance tracks that support both, immune cell migration and density and resulted in tissue-mediated modulation of immune function. Thus, dynamic intravital multiphoton microscopy reveals novel microenvironmental niches and mechanisms that control cancer cell invasion and immune function.