AIM: To investigate the expression of 4-1BB molecule in hepatocellular carcinoma (HCC) and its adjacent tissues. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of 4-1BB in hepatocarcinoma and its adjacent tissues, and peripheral 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 of HCC patients and healthy volunteers, and further to determine whether 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 direct immunofluorescence cytochemical staining and detected by confocal microscopy. RESULTS: 4-1BB mRNA, which was not detectable in normal liver, 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 cm away from tumor edge. In PBMCs, 4-1BB mRNA was almost not detected. Percentage of CD4+, CD8+ and CD3+/CD25+ T cells, as well as ratio of CD4 to CD8 revealed no difference between groups (P>0.05, respectively), while a significant lower percentage of CD3+ T cell was found in HCC group as compared to healthy control group (P<0.05). However, 4-1BB molecules 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+ and 4-1BB+/CD8+ immunofluorescence on tumor infiltrating T cells was detected in 13 liver tissues adjacent to tumor edge (<1.0 cm) by confocal microscopy. CONCLUSION: Although HCC may escape from immune attack by weak immunogenicity or downregulated expression of MHC-1 molecules on the tumor cell surface, tumor infiltrating T cells can be activated via other costimulatory signal pathways to exert a limited antitumor effect on local microenvironment. The present study also implicates that modulating 4-1BB/4-1BBL costimulatory pathway may be an effective immunotherapy strategy to augment the host response.
AIM: To investigate the expression of 4-1BB molecule in hepatocellular carcinoma (HCC) and its adjacent tissues. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of 4-1BB in hepatocarcinoma and its adjacent tissues, and peripheral 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 of HCC patients and healthy volunteers, and further to determine whether 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 direct immunofluorescence cytochemical staining and detected by confocal microscopy. RESULTS:4-1BB mRNA, which was not detectable in normal liver, 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 cm away from tumor edge. In PBMCs, 4-1BB mRNA was almost not detected. Percentage of CD4+, CD8+ and CD3+/CD25+ T cells, as well as ratio of CD4 to CD8 revealed no difference between groups (P>0.05, respectively), while a significant lower percentage of CD3+ T cell was found in HCC group as compared to healthy control group (P<0.05). However, 4-1BB molecules 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+ and 4-1BB+/CD8+ immunofluorescence on tumor infiltrating T cells was detected in 13 liver tissues adjacent to tumor edge (<1.0 cm) by confocal microscopy. CONCLUSION: Although HCC may escape from immune attack by weak immunogenicity or downregulated expression of MHC-1 molecules on the tumor cell surface, tumor infiltrating T cells can be activated via other costimulatory signal pathways to exert a limited antitumor effect on local microenvironment. The present study also implicates that modulating 4-1BB/4-1BBL costimulatory pathway may be an effective immunotherapy strategy to augment the host response.
Authors: A D Santin; P L Hermonat; A Ravaggi; S Bellone; J J Roman; C V Smith; S Pecorelli; A Radominska-Pandya; M J Cannon; G P Parham Journal: Gynecol Obstet Invest Date: 2001 Impact factor: 2.031
Authors: Eddy C Hsueh; Richard Essner; Leland J Foshag; David W Ollila; Guy Gammon; Steven J O'Day; Peter D Boasberg; Stacey L Stern; Xing Ye; Donald L Morton Journal: J Clin Oncol Date: 2002-12-01 Impact factor: 44.544
Authors: B Philosophe; P D Greig; A W Hemming; M S Cattral; I Wanless; I Rasul; N Baxter; B R Taylor; B Langer Journal: J Gastrointest Surg Date: 1998 Jan-Feb Impact factor: 3.452