Stretococcus gordonii

北海道歯学会

北海道歯学雑誌

We have found that the microbial lipopeptide FSL-1, a Toll-like receptor 2（ TLR2） ligand, has the TLR2- mediated anti-tumor activity in vivo. Therefore, we tested the anti-tumor activity in vivo of oral streptococci, because they are known to be recognized by TLR2. On day 0, B16F0 melanoma cells were implanted subcutaneously in the back of C57BL/6 mice of 8-9 weeks of age. Heat-killed and live cells of Streptococcus gordonii were injected into the back of the mice on day 4 and 9 after implantation. Both heat-killed and live S. gordonii significantly inhibited the growth of tumors. As a first step in clarifying the mechanism by which they exhibit anti-tumor activity, the cytotoxic activities of lymphocytes of draining lymph nodes and spleens toward YAC-1 cells as a target （natural killer activity） or B16F0 melanoma cells as a target（ tumor-specific cytotoxic T lymphocyte activity） were therefore measured on day 1 after the second immunization. Natural killer activity was significantly higher in the draining lymph nodes and spleens of the immunized mice. Tumor-specific cytotoxic T lymphocyte activity in spleen of the immunized mice was significantly higher, whereas activity in the draining lymph nodes was also higher, but not significantly. Furthermore, the proportion of Myeloid-Derived Suppressor Cells（ MDSC） and regulatory T cells（ Treg） in the draining lymph nodes was measured by flow cytometry on day 6 after the second immunization. The proportions of both MDSC and Treg were significantly reduced in the immunized mice. Furthermore, Treg was observed around stroma cells and/or transplanted tumor cells in the non-immunized mice, but not in the immunized mice. Taken together, whole cells of S. gordonii had anti-tumor activity in vivo, in which the cytotoxic activities of both tumor-specific cytotoxic T lymphocytes natural killer cells and the upregulation of anti-tumor immune response caused by reduction of the numbers of the immunosuppressor cells such as MDSC and Treg are involved.