Soluble forms of major histocompatibility complex (
MHC) class I-related chain A and B (
MICA/B) are increased in the sera of patients with
malignancy and impair the antitumor immune response by downregulating expression of their cognate immunoreceptor natural killer group 2, member D (NKG2D). Recently, soluble
MICA/B were reported to appear even in some premalignant diseases, raising questions about the impact of soluble
MICA/B produced from
tumors on the expression of NKG2D. The present study examined soluble
MICA/B in chronic
liver disease and
hepatocellular carcinoma (HCC) and their involvement in the immune-cell expression of NKG2D during transcatheter arterial embolization for HCC. The levels of soluble
MICA/B were significantly higher in chronic
liver disease and HCC patients than in healthy volunteers. The progression of
liver disease and that of the
tumor were independent determinants for soluble
MICA/B levels. Immunohistochemistry revealed that
MICA/B were expressed not only in HCC tissue but also on hepatocytes in cirrhotic livers. The transcatheter arterial embolization
therapy significantly decreased serum levels of soluble
MICA, but not soluble MICB, and increased the NKG2D expression on natural killer cells and CD8-positive T cells; there was an inverse correlation between changes in soluble
MICA levels and in NKG2D expression. In conclusion, although soluble
MICA/B are produced from both HCC and premalignant cirrhotic livers, therapeutic intervention for HCC can reduce the levels of soluble
MICA and thereby upregulate the expression of NKG2D.
Cancer therapy may have a beneficial effect on NKG2D-mediated antitumor immunity.