title: Intratumoural administration of dendritic cells: hostile environment and help by gene therapy.
abstract: 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 T cells. 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 environment for artificially released or attracted DCs. This milieu is usually rich in transforming growth factor-beta, vascular endothelial growth factor, and IL-10, -6 and -8, among other substances that diminish DC performance. Several molecular strategies are being devised to interfere with the immunosuppressive actions of these substances and to further enhance the level of anticancer immunity achieved after artificial release of DCs intratumourally.
authors.affiliation: University of Navarra School of Medicine, Gene Therapy Unit, Centro Investigación Médica Aplicada (CIMA), Avda/Pio XII,55, 31080 Pamplona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Huarte
authors.forename: Iñigo
authors.initials: I
authors.lastname: Tirapu
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Arina
authors.forename: María
authors.initials: M
authors.lastname: Vera
authors.forename: Carlos
authors.initials: C
authors.lastname: Alfaro
authors.forename: Oihana
authors.initials: O
authors.lastname: Murillo
authors.forename: Belén
authors.initials: B
authors.lastname: Palencia
authors.forename: Victoria
authors.initials: V
authors.lastname: Busto
authors.forename: Verónica
authors.initials: V
authors.lastname: Marín
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mazzolini
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D004777:Environment; D005818:Genetic Engineering / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000276:immunology*