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

<div>Abstract<p>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 β 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<sup>+</sup> and MHC-II<sup>+</sup>) and CD4<sup>+</sup> and CD8<sup>+</sup> 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<sup>−/−</sup> DCs were recruited to tumors at slightly but significantly higher rate than JAM-A<sup>+/+</sup> DCs. Ablation of CD4<sup>+</sup> and CD8<sup>+</sup> 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. Cancer Res; 70(5); 1759–65</p></div>