Sorting for CCR7-positivity enriches for a dendritic cell population with enhanced antigen-presenting capacity and anti-tumour potency

Abstract

Dendritic cell therapy has been a promising addition to the current armoury of therapeutic options in cancer for more than 20 years but has not yet achieved break-through success. To successfully initiate immunity, dendritic cells have to enter the lymph nodes. However, previous experience of therapeutic dendritic cell administration indicates that this is frequently an extremely inefficient process. The major regulator of dendritic cell migration to the lymph nodes is the chemokine receptor CCR7 and in vitro generated dendritic cells typically display heterogenous expression of this receptor. Here we demonstrate that positive-selection for the dendritic cell subpopulation expressing CCR7 enriches for cells with enhanced lymph node migration and antigen presentation competence as well as a chemokine expression profile indicative of improved interactions with T cells. In models of both subcutaneous and metastatic melanoma we demonstrate that the dendritic cells sorted for CCR7 expression trigger enhanced CD8 T-cell driven antitumour immune responses which correlate with reduced tumour burden and increased survival. Finally we demonstrate that this approach is directly translatable to human dendritic cell therapy using clinical-grade cell sorting.\n\nSynopsisTherapeutic dendritic cells drive anti-cancer immune responses but they migrate inefficiently to lymph nodes. We show that enriching for CCR7 expression yields a dendritic cellular product with enhanced ability to generate immune responses to localised and disseminated tumours.