BACKGROUND/AIMS: The immune response to tumor-specific antigens is typically unable to control the growth and spread of malignant cells. Accumulating evidence indicates that the suppressive effects of CD4+ CD25+ regulatory T-cells are at least partially responsible for the failure of immune-mediated elimination of tumor cells. METHODS: We have studied 25 patients with hepatocellular carcinoma (HCC). The liver tissues with HCC were separated into the marginal region of tumor (peri-tumor region) and the non-tumor region distant from the tumor. CD4+ CD25+ T-cells were quantified in the blood and the liver by flow cytometry and immunohistochemistry, and their effect on T-cell proliferation and activation was determined. RESULTS: We found a significant increase in both the proportion and absolute numbers of CD4+ CD25+ T-cells in the peri-tumor regions, but not in unaffected areas (9.5 +/- 4.5 vs. 4.6 +/- 2.8%, P = 0.011). CD4+ CD25+ T-cells isolated from peri-tumor regions displayed phenotype markers characteristic of regulatory T-cells, and expressed Foxp3 mRNA. CD8+ T-cells in peri-tumor regions were inversely proportional to CD4+ CD25+ T-cells in the same region (P < 0.001). Moreover, isolated CD4+ CD25+ T-cells inhibited autologous CD8+ T-cell proliferation. CONCLUSIONS: Our results suggest that CD4+ CD25+ T-cells in the marginal region of HCC may play a critical role in controlling CD8+ cytotoxic T-cell activity and, thereby, contribute to the progression of HCC.
BACKGROUND/AIMS: The immune response to tumor-specific antigens is typically unable to control the growth and spread of malignant cells. Accumulating evidence indicates that the suppressive effects of CD4+ CD25+ regulatory T-cells are at least partially responsible for the failure of immune-mediated elimination of tumor cells. METHODS: We have studied 25 patients with hepatocellular carcinoma (HCC). The liver tissues with HCC were separated into the marginal region of tumor (peri-tumor region) and the non-tumor region distant from the tumor. CD4+ CD25+ T-cells were quantified in the blood and the liver by flow cytometry and immunohistochemistry, and their effect on T-cell proliferation and activation was determined. RESULTS: We found a significant increase in both the proportion and absolute numbers of CD4+ CD25+ T-cells in the peri-tumor regions, but not in unaffected areas (9.5 +/- 4.5 vs. 4.6 +/- 2.8%, P = 0.011). CD4+ CD25+ T-cells isolated from peri-tumor regions displayed phenotype markers characteristic of regulatory T-cells, and expressed Foxp3 mRNA. CD8+ T-cells in peri-tumor regions were inversely proportional to CD4+ CD25+ T-cells in the same region (P < 0.001). Moreover, isolated CD4+ CD25+ T-cells inhibited autologous CD8+ T-cell proliferation. CONCLUSIONS: Our results suggest that CD4+ CD25+ T-cells in the marginal region of HCC may play a critical role in controlling CD8+ cytotoxic T-cell activity and, thereby, contribute to the progression of HCC.
Authors: Alexander Pedroza-Gonzalez; Guoying Zhou; Ernesto Vargas-Mendez; Patrick Pc Boor; Shanta Mancham; Cornelis Verhoef; Wojciech G Polak; Dirk Grünhagen; Qiuwei Pan; Harry LA Janssen; Gina S Garcia-Romo; Katharina Biermann; Eric Ttl Tjwa; Jan Nm IJzermans; Jaap Kwekkeboom; Dave Sprengers Journal: Oncoimmunology Date: 2015-03-19 Impact factor: 8.110
Authors: Eman R Youness; Mohamed El Nemr; F S Oraby; Nadia M Ahmed; Mohamed A Moghni; Hanan F Aly; Hanaa H Ahmed Journal: Indian J Clin Biochem Date: 2013-09-08