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

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.

• Authors: Masato Murakami, Chiara Francavilla, Ilaria Torselli, Monica Corada, Luigi Maddaluno, Antonio Sica, Gianluca Matteoli, Iliyan Dimitrov Iliev, Alberto Mantovani, Maria Rescigno, Ugo Cavallaro, Elisabetta Dejana
• Journal: Cancer research (Cancer Res) Vol. 70 Issue 5 Pg. 1759-65 (Mar 01 2010) ISSN: 1538-7445 [Electronic] United States
• PMID: 20160037 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules
• F11r protein, mouse
• Receptors, Cell Surface

Topics

• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Carcinoma, Islet Cell (genetics, immunology)
• Cell Adhesion Molecules (deficiency, genetics, immunology)
• Dendritic Cells (immunology)
• Female
• Lymphocytes, Tumor-Infiltrating (immunology)
• Male
• Mice
• Mice, Knockout
• Pancreatic Neoplasms (genetics, immunology)
• Receptors, Cell Surface (deficiency, genetics, immunology)