Basic Rules of T Cell Migration

The positive correlation of lymphocyte infiltration into solid tumors with the patient survival, as well as recent successes of checkpoint inhibitors enhancing antitumor responses, have kindled a huge interest in cancer immunotherapy. In fact, adoptive cell therapy (ACT) of tumor-recognizing T cells has led to complete recession of tumors in a subset of melanoma patients. Yet, the molecular mechanisms that guide T cells to infiltrate tumor tissue for the detection and destruction of cancer cells are only incompletely understood. Here, we will give an overview on the basic rules of T cell migration, focusing on extra- and intracellular guidance cues gained primarily from intravital two photon imaging, and relate this with the efficient unfolding of adaptive immune responses. From this, we outline the challenges that T cells face entering and maneuvering inside non-lymphoid tissues including tumor sites.