Image by Joshua Strokes
Researchers say they have determined how lymphoma cells evade natural killer (NK) cells, and this discovery has revealed potential solutions to the problem.
The team found that NK-cell activation and a second, “triggering” event are both necessary for NK cells to exhibit cytotoxicity in the presence of B-cell lymphoma.
Previous research demonstrated this 2-step process in vitro. Now, researchers have shown that it occurs in vivo.
Dr Ralph Mocikat, of Helmholtz Zentrum München in Munich, Germany, and his colleagues described this research in the European Journal of Immunology.
The team conducted experiments using transplantable tumors, a λ-myc-transgenic model of endogenously arising lymphoma that mimics human Burkitt lymphoma, and mice deficient in the NK group 2 D (NKG2D) receptor.
The experiments showed that NK cells could eliminate lymphoma cells after receiving 2 signals. The first was NK-cell activation, which gave rise to IFN-γ expression.
The researchers found that NK cells could be activated in the presence of MHC class Ilow tumor cells or by injecting bone marrow-derived dendritic cells. Previous research had shown that interleukin 2 (IL-2) and IL-15 could activate NK cells.
The second step involved the NKG2D receptor and its ligands. NKG2D ligands are located on the surface of tumor cells and bind to NK cells. The researchers found that, if these ligands are down-regulated, the NK cells cannot carry out cytotoxic activity.
However, the team found they could increase NKG2D ligand levels. They introduced bortezomib to the tumor cell line 291 and saw a roughly 4-fold increase in NKG2D ligand levels.
“Our results show that the transfer of NK cells is a possible strategic option to treat B-cell lymphoma,” Dr Mocikat said. “According to our findings, this therapeutic approach can be optimized when transferred NK cells are already activated in vitro prior to their injection, thus bypassing the missing activation potential in the tumor microenvironment. An additional injection of IFN-γ or of antibodies against IL-10 could further support the immune activity.”
