AIM:To investigate the expression of 1-1BB molecule inhepatocellular carcinoma (HCC) and its adjacent tissues.METHODS:Reverse transcription-polymerase chain reaction(RT-PCR) was used to determine the gene expression of4-1BB in hepatocarcinoma and its adjacent tissues,andperipheral blood mononuclear cells (PBMCs) from both HCCand health control groups.Flow cytometry was used toanalyse the phenotypes of T cell subsets from the blood ofHCC patients and healthy volunteers,and further to determinewhether 4-1BB molecules were also expressed on the surfaceof CD4+ and CD8+ T cells.The localization of 4-1BB proteinson tumor infiltrating T cells was determined by directimmunofluorescence cytochemical staining and detected byconfocal microscopy.RESULTS:4-1BB mRNA,which was not detectable in normalliver,was found in 19 liver tissues adjacent to tumor edge(<1.0 cm).Low expression of 4-1BB mRNA was shown in 8tumor tissues and 6 liver tissues located within 1 to 5 cmaway from tumor edge.In PBMCs,4-1BB mRNA was almostnot detected.Percentage of CD4~+,CD8~+ and CD3~+/CD25~+ Tcells,as well as ratio of CD4 to CD8 revealed no differencebetween groups (P>0.05,respectively),while a significantlower percentage of CD3~+ T cell was found in HCC group ascompared to healthy control group (P<0.05).However,4-1BBmolecules were almost not found on the surface of CD4+ andCD8+ T cells in HCC and healthy control group.Double-stainingof 4-1BB~+/CD4~+ and 4-1BB~+/CD8~+ immunofluorescence ontumor infiltrating T cells was detected in 13 liver tissuesadjacent to tumor edge (<1.0 cm) by confocal microscopy.CONCLUSION:Although HCC may escape from immuneattack by weak immunogenicity or downregulated expressionof MHC-1 molecules on the tumor cell surface,tumorinfiltrating T cells can be activated via other costimulatorysignal pathways to exert a limited antitumor effect on localmicroenvironment.The present study also implicates thatmodulating 4-1BB/4-1BBL costimulatory pathway may bean effective immunotherapy strategy to augment the hostresponse. AIM: To investigate the expression of 1-1BB molecule in hepatocellular carcinoma (HCC) and its adjacent tissues. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of4-1BB in hepatocarcinoma and its adjacent tissues , andperipheral blood mononuclear cells (PBMCs) from both HCC and health control groups. Flow cytometry was used to analyse the phenotypes of T cell subsets from the blood ofHCC patients and healthy volunteers, and further determinewhether 4-1BB molecules were also expressed on the surface of CD4 + and CD8 + T cells. The localization of 4-1BB proteins on tumor infiltrating T cells was determined by directimmunofluorescence cytochemical staining and detected byconfocal microscopy .RESULTS: 4-1BB mRNA, which was not detectable in normalliver, was found in 19 liver tissues adjacent to tumor edge (<1.0 cm). Low expression of 4-1BB mRNA was shown in 8 tumor tissues and 6 liver tissues located within 1 to 5 cmaway from tumor edge. In PBMCs, 4-1B B mRNA was almost detected (P> 0.05, respectively), while a significant percentage of CD4 ~ +, CD8 ~ + and CD3 ~ + / CD25 ~ CD3 ~ + T cell was found in HCC group ascompared to healthy control group (P <0.05) .However, 4-1BBmolecules were almost not found on the surface of CD4 + and CD8 + T cells in HCC and healthy control group. Double-staining of 4- 1BB ~ + / CD4 ~ + 4-1BB ~ + / CD8 ~ + immunofluorescence on tumor infiltrating T cells was detected in 13 liver tissuesadjacent to tumor edge (<1.0 cm) by confocal microscopy.CONCLUSION: Although HCC may escape from immuneattack by weak immunogenicity or downregulated expression of MHC-1 molecules on the tumor cell surface, tumor infiltrating T cells can be activated via other costimulator pathways to exert a limited antitumor effect on local microenvironment. The present study also implicates that modulating 4-1BB / 4-1BBL costimulatory pathway may bean effective immunotherapy strategy to augment the hostresponse.