For a number of cancers, including neuroblastoma (the second most common tumor in children), tumor infiltration by a subset of immune cells known as V-alpha-24-invariant NKT cells is associated with a favorable outcome. But how these cells have an anticancer effect is unclear, as many tumors do not express the protein that V-alpha-24-invariant NKT cells target.
However, Leonid Metelitsa and colleagues, at the University of Southern California Keck School of Medicine, and The Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, have now shown, in vitro and in mice, that human V-alpha-24-invariant NKT cells indirectly affect neuroblastoma growth by killing tumor-associated cells that promote the growth of neuroblastoma cells.
In the study, human tumor-associated cells known as monocytes/macrophages were found to produce the soluble factor IL-6, which further analysis revealed stimulates the growth of neuroblastoma cells in vitro and after they have been transplanted into mice.
As expected, human V-alpha-24-invariant NKT cells did not kill neuroblastoma cells in vitro, but they did kill monocytes pulsed with tumor antigens. Consistent with this, the growth of neuroblastoma cells was substantially impaired in mice infused with monocytes and V-alpha-24-invariant NKT cells, when compared to mice only receiving monocytes.
These data therefore provide insight into a mechanism by which V-alpha-24-invariant NKT cells can impact cancer outcome.
- V-alpha-24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages in mice and humans. Journal of Clinical Investigation, May 1, 2009
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