Inactivation of Junctional Adhesion Molecule-A Enhances Antitumoral Immune Response by Promoting Dendritic Cell and T Lymphocyte Infiltration

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 ag- gressiveness of pancreatic islet cell carcinoma induced by SV40 T antigen expression in β cells (Rip1Tag2 mice) are significantly reduced in JAM-A-null mice. Because these tumor cells do not express JAM-A, we fo- cused on changes in stroma reactivity. In the absence of JAM-A, tumors showed a small but significant reduc- tion 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 re- cruited 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 de- velopment by increasing antitumor immune response. Cancer Res; 70(5); 1759-65. ©2010 AACR.