Intratumoural administration of dendritic cells: hostile environment and help by gene therapy.

Like paratroopers in special operations, dendritic cells (DCs) can be deployed behind the enemy borders of malignant tissue to ignite an antitumour immune response. ‘Cross-priming T cell responses’ is the code name for their mission, which consists of taking up antigen from transformed cells or their debris, migrating to lymphoid tissue ferrying the antigenic cargo, and meeting specific Tcells. This must be accomplished in such an immunogenic manner that specific T lymphocytes would mount a robust enough response as to fully reject the malignancy. To improve their immunostimulating activity, local gene therapy can be very beneficial, either by transfecting DCs with genes enhancing their performance, or by preparing tumour tissue with pro-inflammatory mediators. In addition, endogenous DCs from the tumour host can be attracted into the malignant tissue following transfection of certain chemokine genes into tumour cells. On their side, tumour stroma and malignant cells set up a hostile immunosuppressive env...