| First Author | Chan CJ | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 2 | Pages | 902-11 |
| PubMed ID | 20008292 | Mgi Jnum | J:159408 |
| Mgi Id | MGI:4442555 | Doi | 10.4049/jimmunol.0903225 |
| Citation | Chan CJ, et al. (2010) DNAM-1/CD155 interactions promote cytokine and NK cell-mediated suppression of poorly immunogenic melanoma metastases. J Immunol 184(2):902-11 |
| abstractText | 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. |
