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

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

Research output: Contribution to journalArticle

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 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 + 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.

Original languageEnglish
Pages (from-to)1759-1765
Number of pages7
JournalCancer Research
Volume70
Issue number5
DOIs
Publication statusPublished - Mar 1 2010

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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