الفهرس 
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Abstract
Tumor microenvironment in hepatocellular carcinoma
(HCC) plays an important role in the establishment and
progression of tumors through immunity and inflammation
mediated by lymphocytes. Many recent therapeutic
interventions are necessary to improve the treatment of HCC
including immunotherapy, which seems to offer one of the
new realistic therapeutic modalities. Several trials are
nowadays performed for immune-restoration against the
immune suppressive action of cancer cells.
This study aims to investigate the optimization of
immunotherapy for HCC patients by appraisal of both
interferon gamma (IFN-γ) levels and phenotyping of
lymphocytes obtained from heparinized peripheral blood
(HPB) and fine-needle aspirates (FNA).
Lymphocytes were isolated from FNA and HPB of 28
HCC patients at National Cancer Institute, Cairo, Egypt. Cells
were cultured in the presence of interleukins IL-2, IL-4 and
IL-12. Enzyme-linked immunosorbent assay (ELISA) and
flow cytometric techniques were used for the assessment of
human IFN-production in the culture supernatants and the
studied T-cell sub-populations respectively. This study also
included 10 healthy subjects as controls.
Mixed cell populations of peripheral blood lymphocytes
(PBLs) and tumor infiltrating lymphocytes (TILs) responded
better than autologous PBLs to mixed stimulatory cytokines;
where the subsequent addition of IL-12 to IL-2 showed a good
enhancement in IFN- secretion, CD4+ & CD8+ cells
productions and an inhibitory effect on CD4+CD25+ regulatory
T-cells (Tregs). Meanwhile, IL-2 plus IL-4 treatment possessed
non-significant effects. IFN- levels were directly correlated
with CD8+ cells during the co-treatment of IL-2+IL-4 and
directly correlated with cell count during the co-treatment of
IL-2+IL-12.
In Conclusion, IL-12 together with IL-2 caused
a suppression of CD4+CD25+ Tregs and an elevation of IFN-γ
levels which play a crucial role for a proper immunotherapy in
the management of patients with HCC.
It is recommended to evaluate this experiment using
a mixed cell populations of TILs and PBLs in the presence of
IL-2 and IL-12 treatment as a promising biotherapy against
cancer cells.