The central nervous system shows tolerance for activated host immune reactions, and this relative unresponsiveness may lessen the efficacy of an
immunotherapy for
brain tumors. Using
interleukin-2 (IL-2)-producing 9L rat
gliosarcoma cells (9L/IL-2), we examined whether secretion of
IL-2 from subcutaneous (s.c.) and/or intracerebral (i.c.)
tumors can elicit augmented immunological responses to
brain tumors. Syngeneic rats could reject 9L/IL-2 cells inoculated s.c., but developed 9L/IL-2
brain tumors by i.c. inoculation. The growth of i.c. 9L/IL-2
tumors was, however, significantly retarded compared with that of i.c. wild-type
tumors. The growth of i.c. wild-type
tumors was significantly suppressed when the rats concurrently received 9L/IL-2 cells s.c. Moreover, most of the rats that were inoculated i.c. with 9L/IL-2 cells did not develop
brain tumors when concurrently injected s.c. with 9L/IL-2 cells. Immunohistochemical analysis on i.c. 9L/IL-2
tumors, when the rats were concurrently inoculated s.c. with 9L/IL-2 cells, revealed that migration of CD4+ or CD8+ T cells, monocytes/microglias, and macrophages was markedly augmented to a similar level as found in the s.c. 9L/IL-2
tumors. These results showed that systemic immune responses to
brain tumor were induced in an immunologically privileged site by concurrent s.c. inoculation of the same
tumors that produce
IL-2. The present study may also raise the possibility of a therapeutic strategy for
brain tumors by the combinatory expression of
IL-2 gene using s.c. immunization followed by direct gene transfer into
brain tumors.