Title: Inactivation of junctional adhesion molecule-A enhances antitumoral immune response by promoting dendritic cell and T lymphocyte infiltration
Authors: Murakami, Masato ×
Francavilla, Chiara
Torselli, Ilaria
Corada, Monica
Maddaluno, Luigi
Sica, Antonio
Matteoli, Gianluca
Iliev, Iliyan Dimitrov
Mantovani, Alberto
Rescigno, Maria
Cavallaro, Ugo
Dejana, Elisabetta #
Issue Date: Mar-2010
Publisher: Waverly Press
Series Title: Cancer Research vol:70 issue:5 pages:1759-1765
Abstract: Junctional adhesion molecule-A (JAM-A)-null dendritic cells (DCs) are more motile and effective than their wild-type counterpart in promoting contact hypersensitivity reaction. Here, we show that the growth and aggressiveness of pancreatic islet cell carcinoma induced by SV40 T antigen expression in beta cells (Rip1Tag2 mice) are significantly reduced in JAM-A-null mice. Because these tumor cells do not express JAM-A, we focused on changes in stroma reactivity. In the absence of JAM-A, tumors showed a small but significant reduction in angiogenesis and a marked increase in the immune reaction with enhanced infiltration of DCs (CD11c+ and MHC-II+) and CD4+ and CD8+ lymphocytes. In contrast, phagocyte number was not affected. DC capacity to produce cytokines was not significantly altered, but transmigration through JAM-A-null endothelial cells was increased as compared with JAM-A-positive endothelium. On adoptive transfer, JAM-A(-/-) DCs were recruited to tumors at slightly but significantly higher rate than JAM-A(+/+) DCs. Ablation of CD4+ and CD8+ cells with specific antibodies abrogated the inhibitory effect of JAM-A deletion on tumor growth and angiogenesis. These findings support the idea that, in the Rip1Tag2 tumor model, abrogation of JAM-A reduces cancer development by increasing antitumor immune response.
ISSN: 0008-5472
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

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