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Inactivation of junctional adhesion molecule-A enhance antitumoral immune response by promoting dendritic cell and T lymphocyte infiltration


Details
Publication Date: 
16/02/2010
Authors: 
Murakami M, Francavilla C, Torselli I, Corada M, Maddaluno L, Sica A, Matteoli G, Iliev ID, Mantovani A, Rescigno M, Cavallaro U, Dejana E
Citation: 
Cancer Res. 2010 Mar 1;70(5):1759-65 [Epub 2010 Feb 16]
DOI: 
10.1158/0008-5472.CAN-09-1703
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.