FLT3 ligand expressing adenoviral vectors promote anti-tumor immunity and improve survival in a glioblastoma model

CURTIN; XIONG; KING; ZIRGER; PUNTEL; LIU; LOWENSTEIN; CASTRO

San Diego, California, USA

Congreso; American Society of Gene Therapy; 2003

The lack of professional afferent APCs in naive brain parenchyma contributes to the systemic immune ignorance to Ags localizedexclusively within the brain. Dendritic cells (DCs) appear within the brain as a consequence of inflammation, but no molecularmechanisms accounting for this influx have been described. In this study we demonstrate that Fms-like tyrosine kinase 3 ligand(Flt3L) recruits plasmacytoid DCs (pDCs; >50-fold; p < 0.001) to the brain parenchyma. These pDCs expressed IFN-, thehallmark cytokine produced by pDCs, indicating recruitment and activation in situ of bona fide pDCs within the brain parenchyma.Flt3L did not increase the numbers of conventional DCs, macrophages, or B, T, NK, NKT, or microglial cells within thebrain. Our data demonstrate that Flt3L reconstitutes a crucial afferent component of the immune response, namely, professionalAPCs within the brain parenchyma, and this could counteract the intrinsic systemic immune ignorance to Ags localized exclusivelywithin the brain.