Fig. 1. Tissue immunity determines metastatic progression.

Before metastases manifest themselves clinically, tumour cells need to overcome multiple barriers throughout their journey from the primary site until they successfully colonize a distant site. First, they invade locally and intravasate the endothelium to enter the circulation, where they travel alone or in clusters with other cells, in search of a new site to extravasate and expand. The few disseminated tumour cells (DTCs) that survive the journey then face attrition from the specific immune environment within the distant site: where antimetastatic tissue-resident immune cell populations are dominant, DTCs blend into the physiological context and persist in a quiescent state for several years or even decades (dormancy stage of cancer); conversely, microenvironments depleted of antimetastatic immune cells or enriched in other immune cells conducive to DTC reactivation support metastatic outgrowth into clinically detectable metastases. Treating the specific immune microenvironment at distant sites may be a way to effectively control DTCs. DC, dendritic cell; ILC, innate lymphoid cell; NK, natural killer.