Cell migration is a pivotal process in immunity. Indeed, appropriate immune responses (i.e. efficient but not detrimental to the host) rely on the coordinated actions of multiple cellular players. Each immune cell needs to be at the right place at the right time and be able to navigate within a tissue but also between organs to sustain immunity. Over the past years, we have been investigating how the physical properties of the microenvironment are impacting immune cell trajectories as well as local accumulation. In particular, we have demonstrated how macropinocytosis (the capacity of engulfing large amount of fluid) renders dendritic cells, the sentinels of the immune systems, insensitive to the surrounding hydraulic resistance, and how this specific feature may contribute to their immune function. We also reported that physical properties of the microenvironment (namely confinement) do not only impact migration but also dendritic cell maturation and control the amplitude of the immune response. More recently, we have uncovered that T cells and neutrophils have distinct topographical preferences, which dictates their infiltration of tumors. We are now investigating the underlying mechanisms using synthetic fibrillar systems of controlled topography and stiffness.