| First Author | Brenner CD | Year | 2010 |
| Journal | Eur J Immunol | Volume | 40 |
| Issue | 2 | Pages | 494-504 |
| PubMed ID | 19950185 | Mgi Jnum | J:157674 |
| Mgi Id | MGI:4431336 | Doi | 10.1002/eji.200939937 |
| Citation | Brenner CD, et al. (2010) Requirements for control of B-cell lymphoma by NK cells. Eur J Immunol 40(2):494-504 |
| abstractText | The role of NK cells in the control of endogenously arising tumors is still unclear. We monitored activation and effector functions of NK cells in a c-myc-transgenic mouse model of spontaneously arising lymphoma. At early stages, tumors demonstrated reduced MHC class I expression and increased expression of natural killer group 2D ligands (NKG2D-L). NK cells in these tumors showed an activated phenotype that correlated with the loss of tumor MHC class I. With increasing tumor load however, NK-cell effector functions became progressively paralyzed or exhausted. In later stages of disease, tumors re-expressed MHC class I and lost NKG2D-L, suggesting a role of these two signals for NK cell-mediated tumor control. Testing a panel of lymphoma cell lines expressing various MHC class I and NKG2D-L levels suggested that NK cell-dependent tumor control required a priming and a triggering signal that were provided by MHC class I down-regulation and by NKG2D-L, respectively. Deleting either of the 'two signals' resulted in tumor escape. At early disease stages, immune stimulation through TLR-ligands in vivo efficiently delayed lymphoma growth in a strictly NK cell-dependent manner. Thus, NK-receptor coengagement is crucial for NK-cell functions in vivo and especially for NK cell-mediated tumor surveillance. |
