The activating
receptor NKG2D (natural killer group 2, member D) of natural killer (NK) cells promotes
tumor immune surveillance by targeting
ligands selectively induced on
cancer cells, and thus having an important role in antitumor immune response. Because these
ligands are not widely expressed on healthy adult tissue, NKG2D
ligands may present as useful target for immunotherapeutic approaches in
cancer. In this study, to elucidate the role of NKG2D-NKG2D
ligand interaction in
thymoma tissues and to evaluate the potential role of NKG2D
ligands as therapeutic target for
thymoma, we examined the expression of NKG2D and its specific
ligands:
MICA (major histocompatibility complex class I chain-related
protein A), MICB (major histocompatibility complex class I chain-related
protein B) and ULBP (UL16-binding protein) in 36
thymomas (6 subtype A, 6 subtype AB, 8 subtype B1, 5 subtype B2, 6 subtype B3 and 5 subtype C), 15 thymic
atrophy and 8
thymic hyperplasia by immunohistochemistry and reverse transcription-real-time-PCR methods. We demonstrated that both
mRNA and
protein levels of NKG2D,
MICA, MICB and ULBP were upregulated in six types of
thymomas compared with those in atrophic thymus or proliferating thymus. Furthermore, the NKG2D
ligands were found to be frequently coexpressed on
thymoma cells. Furthermore, the expression of
MICA, MICB and ULBP in subtype C was higher compared with those in subtype A, AB, B1, B2 and B3. Thus, we concluded that high expressions of NKG2D,
MICA, MICB and ULBP1 were shown in patients with
thymoma, and this may enhance the recognition function of NK cells to eliminate
tumor cells.
MICA, MICB and ULBP presented an attractive target for
thymoma therapy. The abnormal expression of NKG2D,
MICA, MICB and ULBP1 can provide us with evidence of the occurrence of
thymoma and could also be used as a target in the treatment of
thymoma.