Immunotherapy of gliomas has been forwarded as an attractive alternative to standard therapeutic modalities. Numerous observations indicate some therapeutic efficacy with this approach, but it is not curative in most reports. It is well established that gliomas suppress immune reactivity via a number of mechanisms, including expression CD95 ligand (CD95L), which induces apoptosis of immune effector cells, and secretion of immunosuppressive factors such as transforming growth factor-beta (TGFβ). It has been hypothesized that abrogation of production or function of TGFβ would improve immune reactivity to gliomas. To investigate this in a fashion that is translatable into clinical practice, we utilized a retroviral vector encoding a truncated, soluble form of the Type II receptor for TGFβ (TFGβsr) and expressed it in the rat 9L gliosarcoma line (9L-TGFβsr). We then determined whether expression of TGFβsr affected in vitro sensitivity of 9L to lysis by immune effector cells, whether expression of TGFβsr affected tumorigenesis of 9L in vivo, and whether TGFβsr affected expression of immunity to 9L. In these experiments, we determined that 9L-TGFβsr was more susceptible than sham transfected 9L (9L-neo) to lysis by natural killer (NK) cells. We also determined that subcutaneously implanted 9L-TGFβsr was less tumorigenic than 9L-neo in syngeneic rats. Similarly, survival was extended by ∼40% in rats given intracranial 9L-TGFβsr compared to 9L-neo. Finally, we determined that elimination of CD161+ cells resulted in comparable growth of 9L-neo and 9L-TGFβsr in vivo, indicating that NK or NK-like cells were responsible for the anti-tumor effects in this model.