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

TitleInactivation of junctional adhesion molecule-A enhances antitumoral immune response by promoting dendritic cell and T lymphocyte infiltration.
Publication TypeJournal Article
Year of Publication2010
AuthorsMurakami M, Francavilla C, Torselli I, Corada M, Maddaluno L, Sica A, Matteoli G, Iliev ID, Mantovani A, Rescigno M, Cavallaro U, Dejana E
JournalCancer Res
Volume70
Issue5
Pagination1759-65
Date Published2010 Mar 1
ISSN1538-7445
KeywordsAnimals, 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.

DOI10.1158/0008-5472.CAN-09-1703
Alternate JournalCancer Res.
PubMed ID20160037
Grant ListE.1254 / / Telethon / Italy

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