Title | Inactivation of junctional adhesion molecule-A enhances antitumoral immune response by promoting dendritic cell and T lymphocyte infiltration. |
Publication Type | Journal Article |
Year of Publication | 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 |
Journal | Cancer Res |
Volume | 70 |
Issue | 5 |
Pagination | 1759-65 |
Date Published | 2010 Mar 1 |
ISSN | 1538-7445 |
Keywords | Animals, Carcinoma, Islet Cell, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Adhesion Molecules, Dendritic Cells, Female, Lymphocytes, Tumor-Infiltrating, Male, Mice, Mice, Knockout, Pancreatic Neoplasms, Receptors, Cell Surface |
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. |
DOI | 10.1158/0008-5472.CAN-09-1703 |
Alternate Journal | Cancer Res. |
PubMed ID | 20160037 |
Grant List | E.1254 / / Telethon / Italy |
Submitted by alp2017 on April 1, 2016 - 3:46pm