Killer targets in metastasis

An international team has found a new pathway in NK cells that leads to the rejection of metastatic tumors.1 It is still unclear which components of the pathway will make the best targets.

The pathway centers around an E3 ubiquitin ligase called casitas B cell lymphoma-b (CBL-B) that is known to negatively regulate T cells.2 In 2007, a group led by Josef Penninger showed that Cbl-b knockout resulted in CD8+ T cell-mediated tumor rejection in several mouse models.3

In the following years, the group pursued strategies to target Cbl-b in T cells and understand the mechanism of Cbl-b activity in T cells. In a new study, an international team led by Penninger observed a curious result-Cbl-b knockouts that lacked T cells also rejected tumors. Penninger is senior scientist and scientific director of the Institute of Molecular Biotechnology of the Austrian Academy of Sciences.

That finding prompted Penninger to hypothesize that Cbl-b also must be operational elsewhere in the immune system and led his group to uncover NK cells as the mysterious other cell type in a CBL-B-dependent pathway that suppresses activity (see "Strategies to

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