Inhibition of experimental rat glioma growth by decorin gene transfer is associated with decreased microglial infiltration

Decorin gene therapy for experimental malignant glioma is thought to involv e antagonism of immunosuppression induced by glioma-derived transforming gr owth factor-beta (TGF-beta). TGF-beta is chemotactic for cells of the monoc yte macrophage lineage but inhibits their functional activity in many in vi tro paradigms. Here, we examined changes in the patterns of microglial infi ltration of rat C6 gliomas expressing a decorin transgene. We find that the number of OX42/ED-l-positive microglial cells is reduced rather than enhan ced in the presence of decorin. Decorin-expressing gliomas contain lower nu mbers of MHC class II antigen-expressing microglial cells whereas the relat ive frequency of MHC I immunoreactivity among microglial cells is increased . Interestingly, the reduction of TGF-beta levels in the tumors by decorin is associated with the de novo expression of inducible nitric oxide synthas e (iNOS) in a minority of microglial cells. These data suggest that microgl ial cells do not participate in the regression of decorin-expressing rat C6 gliomas. (C) 1999 Elsevier Science B.V. All rights reserved.