Abstracts (complete list) - Wissenschaft Online

Matthias Krusch, Tina Baessler, Katrin Miriam Baltz, Helmut Rainer Salih
CD137 ligand expression on acute myeloid leukemia cells
modulates immune surveillance of human NK cells identified
to express CD137 upon activation
Studies of haploidentical bone marrow transplantation (BMT) suggest that NK cells play
an important role in immunosurveillance of leukemia, and acute lymphoblastic
leukemias (ALL) were shown to be less susceptible to NK-mediated lysis than acute
myeloid leukemia (AML). NK cell reactivity is governed by a balance of activating and
inhibitory receptors including various members of the TNF receptor (TNFR) family. The
TNFR family member CD137/4-1BB has been shown to stimulate proliferation and IFN-γ
production, but not cytotoxicity of NK cells in mice. Surprisingly, yet nothing is known
regarding the consequences of CD137-CD137 ligand (CD137L) interaction for NK cell
reactivity in humans. Here we report that NK cells express CD137 upon stimulation with
activating cytokines like IL-2 or IL-15. In addition, we demonstrate that primary acute
myeloid leukemia (AML) cells of patients express CD137L in 14 of 34 (41%) cases.
CD137L expression in AML was not associated with expression of HLA-class I, CD80/86
or ligands for the activating immunoreceptor NKG2D. Reverse signaling via CD137L into
AML cells induced the release of the immunoregulatory cytokines IL-10 and TNF.
Furthermore, AML-expressed CD137L stimulated both cellular cytotoxicity and IFN-γ
production of CD137-expressing NK cells, since NK cell reactivity was significantly
reduced by addition of blocking CD137 antibodies in coculture assays. Taken together,
our data indicate that CD137 is inducibly expressed and mediates different effects in
human compared to murine NK cells. Furthermore, CD137L expression substantially
influences tumor immunoediting by AML cells and modulates NK cell-mediated
immunosurveillance of leukemia.