ABSTRACT
Although there is convincing data in support of the effectiveness of hyperthermia in tumor therapy, the molecular mechanisms underlying the clinical effects of hyperthermia are still poorly understood. To investigate natural killer [NK] cell cytotoxicity against heat-treated SW-872 and HeLa tumor cell lines. NKG2D ligands and HLA class I transcription were examined using quantitative real-time PCR in treated tumor cell lines at 0, 2, 4, 6 and 12 h following thermal treatment at 39 Degree °C and 42 Degree °C for 1 h. The expression of MICA/B, ULBP1 and ULBP2 were also determined by flow cytometry. NK92-MI cytotoxic activity against heat-treated target cell lines was assessed by LDH release as well as annexin-V and 7-AAD assays. Our results showed that heat treatment at 39°C improved the cytolytic activity of NK cells against SW-872 cells without increasing NKG2D ligand concentration or decreasing HLA class I levels. The observed increase in the cytotoxicity of NK cells against SW-872 cells after hyperthermia does not coincide with changes in MICA/B, ULBP1 and ULBP2 ligands of NKG2, however, the expression of other ligands in target cells may have made the cells susceptible to the cytotoxic effect of NK cells
ABSTRACT
A possible mechanism by which hyperthermia enhances tumor immunogenicity is the induction of NKG2D ligands on tumor cells. Although the expression of MHC class I chain-related protein A and B [MICA/B] has previously been reported in different carcinomas, there is no information about MICA/B expression in liposarcomas. To investigate MICA/B induction in a human liposarcoma cell line [SW-872] after thermotherapy. SW-872 and HeLa cell lines were subjected to thermal stress for 1 h at 42, 44 and 46[degree sign]C, and after 2, 4 and 6 h of incubation at 37[degree sign]C, MICA/B expression was assessed at the mRNA and protein levels. Despite high levels of MICA/B transcripts in SW-872 cells at baseline, the expression of these genes decreased significantly at both the mRNA and protein levels after almost all thermal treatments. Our data conclude that thermotherapy under 42-46[degree sign]C had no effect on MICA/B induction on SW-872 liposarcoma cell line but the effects of fever-range temperatures remain to be tested on this cell line