PT  - JOURNAL ARTICLE
AU  - Chan, Christopher J.
AU  - Andrews, Daniel M.
AU  - McLaughlin, Nicole M.
AU  - Yagita, Hideo
AU  - Gilfillan, Susan
AU  - Colonna, Marco
AU  - Smyth, Mark J.
TI  - DNAM-1/CD155 Interactions Promote Cytokine and NK Cell-Mediated Suppression of Poorly Immunogenic Melanoma Metastases
AID  - 10.4049/jimmunol.0903225
DP  - 2010 Jan 15
TA  - The Journal of Immunology
PG  - 902--911
VI  - 184
IP  - 2
4099  - http://www.jimmunol.org/content/184/2/902.short
4100  - http://www.jimmunol.org/content/184/2/902.full
SO  - J. Immunol.2010 Jan 15; 184
AB  - 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.