Trafficking of Dendritic Cells in the Tumor Environment

To initiate immune responses, dendritic cells follow a migratory route from their recruitment as sentinels into tissues, including solid tumors, then to secondary lymphoid organs where they contour the immune response. Migratory capacities and chemokine responsiveness are therefore key elements in dendritic cell immunobiology. Tumor-derived factors alter dendritic cell maturation and function and thus markedly affect dendritic cell trafficking and distribution. Tumor-mediated down-regulation or redirection of dendritic cell migration and homing may markedly alter a normal pattern of dendritic cell localization and thus induction of antitumor immunity in tumor-bearing hosts, and might also strongly inhibit the efficacy of dendritic cell vaccines. Improved understanding of the regulation of DC trafficking might offer new opportunities for therapeutic interventions to control immune responses. Given the current interest in applying dendritic cell-based immunotherapy to cancer treatment, an understanding of the molecular defects responsible for dysfunction of dendritic cell trafficking and biodistribution in cancer is essential for designing and testing the next generation of dendritic cell vaccines.