Expression of a soluble transforming growth factor-beta (TGFbeta) receptor reduces tumorigenicity by regulating natural killer (NK) cell activity against 9L gliosarcoma in vivo.

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 (TGFbeta).

Glioma-associated hyaluronan induces apoptosis in dendritic cells via inducible nitric oxide synthase: implications for the use of dendritic cells for therapy of gliomas.

As a means of enhancing immunity to gliomas, we investigated local delivery of rat, bone marrow-derived dendritic cells (DCs) into rat 9L gliosarcoma tumors and into 9L tumors induced to undergo apoptosis by gamma knife radiosurgery. Contrary to other tumors, local delivery of DCs had no therapeutic effect on 9L gliomas, even when tumor apoptosis was induced via radiosurgery, which leads to efficient "loading" of the DCs with tumor antigen. To determine whether antigen-presenting cells, such as DCs, were viable in tumors, we carried out multiparametric staining of 9L tumors, using phycoerythrin-conjugated OX6 (MHC class II) or OX62 (DC specific) and FITC-labeled Val-Ala-Asp-fluoromethyl ketone (FITC-VAD-FMK; activated caspases).