An essential role of immune cells as extrinsic tumor suppressor has been demonstrated. However, immune cells in the tumor microenvironment not only fail to mount an effective antitumor immune response, but also interact intimately with the transformed cells to promote oncogenesis actively. We and others have demonstrated that Stat3, a key oncogenic transcription factor constitutively activated in diverse cancer cells and important for tumor cell survival and invasion, is also activated in tumor stromal immune cells and potently immunosuppressive. Constitutively-activated Stat3 inhibits the expression mediators necessary for immune activation against tumor cells. Moreover, Stat3 activity promotes the production of immunosuppressive factors that activate Stat3 in diverse immune cell subsets. Among the immunosuppressive factors regulated by Stat3 are IL-6, IL-23 and IL-17, which are elevated in cancer, promote chronic inflammation, and cancer progression. Many of these immunosuppressive factors are also Stat3 activators. Our recent results further demonstrate that activated Stat3 in tumor myeloid cells, including macrophages and myeloid-derived suppressor cells, is important for mediating tumor angiogenesis. As such, Stat3 propagates several levels of crosstalk between tumor cells and the tumor microenvironment, leading to tumor-induced immunosuppression, tumor survival and tumor angiogenesis.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):PL03-01.
- American Association for Cancer Research