Objective   To study the effects of Sorafenib

a kind of multiple targeted agent

on the distribution and expression of CD68 and CD57

the markers of macrophages and natural killer cell during the course of hepatocellular carcinoma (HCC).     Methods   HCC model was established using improved method. The subjects were divided into six groups: blank control (group A)

HCC model without intervention (group B)

early stage HCC model with single dose of Sorafenib (group C)

early stage HCC model with double dose of Sorafenib (group D)

advanced stage with single dose (group E) and advanced stage with double dose (group F). The dynamic changes in CD57

CD68 and CD34 expressions from HCC tissues were detected immunohistochemically.     Results   Count of CD57 and CD68 positive cells in group B increased gradually

but the count of these cells in groups  C

D

E and F decreased at different degrees after the occurrence of the peak value at 12 and 14 weeks. No obvious change in the count of CD57 and CD68 positive cells was found in groups D and F at 18th week. At 20th and 22nd weeks

CD57 and CD68 positive cells in group D and F increased significantly as compared with those in group B (P0.05)

and the same result was found between groups D and C

groups F and E

and groups D and F (P0.01

P0.05). No significant difference was found between other groups. CD34 positive cells in group B increased gradually

but these cells in groups B

C

D

E and F decreased at 16th week in a time-dependent manner. Significant difference was found between group D and groups C

E and F (P0.05).     Conclusion   Sorafenib can not only inhibit angiogenesis of HCC

but also induce the aggregation of macrophages and natural killer cells in HCC tissues

suggesting there might be a novel dose-dependent immunoregulatory mechanism in the molecular targeted therapy of HCC treatment with Sorafenib.