DNAM-1/CD155 interactions promote cytokine and NK cell-mediated suppression of poorly immunogenic melanoma metastases.

Abstract

A role for NK cells in therapeutic intervention for hematologic malignancies, such as acute myeloid leukemia and multiple myeloma, and nonhematologic malignancies, such as melanoma, is becoming more apparent. DNAM-1 is an NK cell receptor whose importance in facilitating activation signals received by NK cells in natural and cytokine-driven responses to tumor metastases in vivo is poorly explored. In this study, we used matched tumor lines expressing a variety of relevant ligands, neutralizing monoclonal Abs, and DNAM-1 gene-targeted mice to determine the relative importance of DNAM-1-ligand interactions in controlling tumor metastases. Our results demonstrate that NK cells require DNAM-1 for natural or cytokine (IL-2, IL-12, or IL-21) suppression of tumor metastases or their variants expressing CD70 or CD80. In contrast, DNAM-1 was dispensable when tumor cells were targets of Ab-dependent cellular cytotoxicity or presented ligands for NKG2D. CD155 appeared to be a key ligand recognized by DNAM-1 in NK cell-mediated suppression of metastases, and DNAM-1-mediated suppression coincided with perforin activity. Overall, these data implied a general role for DNAM-1-CD155 interactions in NK cell-mediated killing of tumors, even in the presence of tumor CD70 or CD80 expression, and further defined the optimal efficacy requirements of cytokines that directly activate NK cells.

• Authors: Christopher J Chan, Daniel M Andrews, Nicole M McLaughlin, Hideo Yagita, Susan Gilfillan, Marco Colonna, Mark J Smyth
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 184 Issue 2 Pg. 902-11 (Jan 15 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20008292 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Differentiation, T-Lymphocyte
• B7-1 Antigen
• CD226 antigen
• CD27 Ligand
• Cytokines
• Ligands
• Receptors, Virus
• poliovirus receptor

Topics

• Animals
• Antibody-Dependent Cell Cytotoxicity
• Antigens, Differentiation, T-Lymphocyte (immunology, metabolism)
• B7-1 Antigen
• CD27 Ligand
• Cell Line, Tumor
• Cytokines (immunology)
• Killer Cells, Natural (immunology)
• Ligands
• Melanoma, Experimental (immunology, pathology)
• Mice
• Neoplasm Metastasis (immunology)
• Receptors, Virus (immunology, metabolism)