MABF2349-25UL Sigma-AldrichAnti-PVR (CD155) Antibody, clone TX56

Emerging evidence suggests that DNAM-1 (CD226) play an important role in the recognition of tumor cells and their lysis by cytotoxic T lymphocytes (CTL) and NK cells. Although the DNAM-1 ligand CD155 is ubiquitously expressed in various tissues, many human tumors significantly upregulate the expression of CD155; DNAM-1 on CTL and NK cells may be involved in tumor immunity. However, unlike those in mice, human tissues also express soluble isoforms of CD155 (sCD155) that lack the transmembrane region. Here, we show that sCD155 levels were significantly higher in the sera of 262 patients with lung, gastrointestinal, breast, and gynecologic cancers than in sera from healthy donors. In addition, the sCD155 levels were significantly higher in patients with early stage (stages 1 and 2) gastric cancer than in healthy donors, and were significantly higher in patients with advanced stage (stages 3 and 4) disease than in patients in those with early stage disease and healthy donors. Moreover, the sCD155 levels were significantly decreased after surgical resection of cancers. Thus, sCD155 level in serum may be potentially useful as a biomarker for cancer development and progression.

Although Th1 and Th2 cells are known to be involved in allergic inflammatory diseases, the molecular mechanisms underlying their differentiation are incompletely understood. In this study, we identified CD155 as a costimulatory molecule on CD4(+) T cells. Importantly, CD155-mediated signaling induced Th1 development in both humans and mice, as evidenced by production of IFN-γ and upregulation of Tbx21 transcription; these effects were independent of IL-12 but dependent on NF-κB-induced autocrine IFN-γ that triggered positive feedback via STAT1 activation. Mice genetically deficient in CD155 or treated with anti-CD155 Ab exhibited attenuated Th1-type contact hypersensitivity. Thus, CD155 plays an important regulatory role in helper T cell differentiation and allergic diseases.

Since the identification of ligands for human and mouse DNAM-1, emerging evidence has suggested that DNAM-1 plays an important role in the T cell- and natural killer (NK) cell-mediated recognition and lysis of tumor cells. However, it remains undetermined whether DNAM-1 is involved in tumor immune surveillance in vivo. We addressed this question by using DNAM-1-deficient mice. DNAM-1-deficient cytotoxic T lymphocyte (CTL) and NK cells showed significantly less cytotoxic activity against DNAM-1 ligand-expressing tumors in vitro than wild-type (WT) cells. The methylcholanthrene (MCA)-induced fibrosarcoma cell line Meth A expressed the DNAM-1 ligand CD155, and DNAM-1-deficient mice showed increased tumor development and mortality after transplantation of Meth A cells. Moreover, the DNAM-1-deficient mice developed significantly more DNAM-1 ligand-expressing fibrosarcoma and papilloma cells in response to the chemical carcinogens MCA and 7,12-dimethylbenz[a]anthracene (DMBA), respectively, than did WT mice. These results indicate that DNAM-1 plays an important role in immune surveillance of tumor development.