PRIMING IN THE BRAIN, AN IMMUNOLOGICALLY PRIVILEGED ORGAN, ELICITS ANTITUMOR IMMUNITY

A crucial question in the study of tumor neuro-immunology concerns the capacity of the central nervous system to initiate and execute an imm une response, In a 100% fatal rat malignant glioma model, genetically modified tumors secreting INF-gamma intracerebrally generate an immune response resulting in a substantial increase in survival time, tumor rejection and specific systemic immunity, Tumors modified to secrete I L-2 alone do not change the biologic behavior of transfected gliomas. INF-gamma induces elevated expression of major-histocompatibility-comp lex-class-I and -class-II molecules in microglia throughout the brain and invokes enhanced tumor infiltration by CD4, CD8 and NK cells. Thes e findings demonstrate successful immunization against a central nervo us-system tumor by direct priming in the brain with a live growth-comp etent tumor vaccine. (C) 1998 Wiley-Liss, Inc.