Vol 49, No 3 (2011)
Original paper
Published online: 2011-10-28
Induction of monocyte antitumor response by human cancer cells transduced with TNF-GFP fusion gene: possible implications for immunotherapy of cancer
DOI: 10.5603/FHC.2011.0072
Folia Histochem Cytobiol 2011;49(3):512-520.
Abstract
This study was undertaken to determine how human pancreatic cancer (HPC-4) cells transduced with
the TNF-GFP fusion gene (TLG) alter the antitumor response of human monocytes in vitro and whether they
could act as an antitumor vaccine. In our model, HPC-4 cells were transduced with retroviral vector harboring
TLG gene and designated as HPC-4TLG. The TLG protein expression was confirmed by Western blot and flow
cytometry analysis. Monocytes were co-cultured with transduced and control HPC-4 cells. The secretion of
TNF, IL-10 and IL-12 was measured by ELISA. The cytotoxicity of monocytes against HPC-4 cells was determined
by MTT test. The results show that the HPC-4TLG cells expressed membrane-bound, intracellular and
secretory TLG protein. When cultured with HPC-4TLG cells, monocytes released a higher amount of TNF, but
IL-10 and IL-12 secretion was inhibited. The pre-exposure of monocytes to HPC-4TLG, but not to HPC-4, cells
did not decrease TNF nor increase IL-10 production, thus not leading to monocyte deactivation. Also, the
antitumor cytotoxicity of monocytes stimulated with HPC-4TLG was not downregulated, which occurred when
non-transduced HPC-4 cells were used. In conclusion, compared to parental HPC-4 cells, TLG gene transduced
HPC-4 cells induced stronger antitumor response of monocytes in vitro and prevented deactivation of monocytes.
(Folia Histochemica et Cytobiologica 2011, Vol. 49, No. 3, 512–520)
Keywords: fusion genemonocytestumor cellstumor necrosis factor
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