Abstract
Dysfunction of the host immune system in cancer patients can be due to a number of factors, including lymphocyte apoptosis. Several studies showed that Foxp3+T cells take part in inducing this process by expressing FasL in tumor patients. However, the relationship between apoptosis, CD8+T cells and Foxp3+T cells in HCC patients is still unclear. The present study was designed to investigate the correlation between apoptosis levels and Fas/FasL expression in CD8+T lymphocytes and Foxp3+T cells in patients with HCC. CD8+T cells and CD3+Foxp3+T cells were tested from peripheral blood of HCC patients and normal controls and subjected to multicolor flow cytometry. The expression of an apoptosis marker (annexin V) and the death receptor Fas in CD8+T cells and FasL in CD3+Foxp3+T cells were evaluated. Serum TGF-β1 levels in patients with HCC were measured by enzyme-linked immunosorbent assay. The relationship between apoptosis and Fas expression, as well as FasL expression in CD3+Foxp3+T cells was then evaluated. The frequency of CD8+T cells binding annexin V and Fas expression in CD8+T cells, were all higher in HCC patients than normal controls and the proportion of apoptotic CD8+T cells correlated with their Fas expression. Serum TGF-β1 levels correlated inversely with CD3+Foxp3+T cells. Fas/FasL interactions might lead to excessive turnover of CD8+T cells and reduce anti-tumor immune responses in patients with HCC. Further investigations of apoptosis induction in Fas+CD8+T cells in vitro are required.
Highlights
Tumor escape from immunological surveillance involve a variety of mechanisms from the downregulation or loss of surface molecules necessary for tumor recognition to deregulation of immune cell functions and/or the induction of apoptosis in effective T cells (Ferrone et al, 2007; Kerkar et al, 2012)
CD8+T cells and CD3+Foxp3+T cells were tested from peripheral blood of HCC patients and normal controls and subjected WRPXOWLFRORUÁRZF\WRPHWU\7KHH[SUHVVLRQRIDQDSRSWRVLVPDUNHU DQQH[LQ9 DQGWKHGHDWKUHFHSWRU)DVLQ CD8+T cells and Fas ligand (FasL) in CD3+Foxp3+7FHOOVZHUHHYDOXDWHG6HUXP7*)ơOHYHOVLQSDWLHQWVZLWK+&&ZHUH measured by enzyme-linked immunosorbent assay
While the Fas/FasL system plays an important role in B and T lymphocyte development and maturation (Rauf et al, 2012), it may serve as a mechanism for LPPXQH HYDVLRQ E\ D YDULHW\ RI QHRSODVPV LQFOXGLQJ ovarian carcinoma, colon cancer, melanoma and glioma .DVVRXIHWDO/LQHWDO 7KHÀHOGRIWXPRU immunology is strongly focused on CD8+T cells in recent \HDUV RZLQJ WR WKHLU DELOLW\ WR GLUHFWO\ NLOO WXPRU FHOOV DQGWKHUHDUHVWURQJDVVRFLDWLRQEHWZHHQWXPRULQÀOWUDWLQJ CD8+T cells and patient survival in many cancers (Pagès et al, 2010)
Summary
Tumor escape from immunological surveillance involve a variety of mechanisms from the downregulation or loss of surface molecules necessary for tumor recognition to deregulation of immune cell functions and/or the induction of apoptosis in effective T cells (Ferrone et al, 2007; Kerkar et al, 2012).
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