Time course analysis and modulating effects of established brain tumor on active-specific immunotherapy.
OBJECTIVE
There have been numerous attempts to establish an effective immunotherapy for the treatment of brain tumors. To date, reliable methods to manipulate the immune system for promoting brain tumor regression have been disappointing. Generation of active immune responses in most of these studies was only possible in the absence of viable tumor cells, suggesting that immunotherapy can only be used as preventive therapy. In few studies the investigators have demonstrated success in using immunotherapy to treat a preestablished intracranial tumor. Using the 9L intracranial glioma model, the authors sought to delineate the underlying mechanisms for these observations.


METHODS
In animals vaccinated with irradiated 9L glioma cells and interferon-gamma 14 and 7 days prior to intracranial tumor cell challenge, a significant increase in survival was shown. In contrast, vaccinations applied 3 days prior to, at the time of (Day 0) or 7 days after intracranial tumor cell challenge failed to influence survival. Histological examination of brain tissue specimens obtained in animals vaccinated before or after tumor cell challenge showed no difference in the degree of peritumoral mononuclear cell infiltration. When activated spleen cells obtained obtained from these animals were assayed for cytotoxicity and proliferative capacity, only those spleen cells derived from animals vaccinated prior to intracranial tumor cell challenge showed enhanced activity.


CONCLUSIONS
These data support the presence of a strong modulatory effect of tumor on local and systemic antitumoral immune response. This immunosuppression appears to be secondary to a direct effect on T-cell function. Reversal of this immunosuppression may be a useful adjunct to tumor vaccine therapy.
Liu
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Department of Neurosurgery, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
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Lillehei
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D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D019496:Cancer Vaccines; D002455:Cell Division / Q000276:immunology; D045744:Cell Line, Tumor / Q000637:transplantation; D018316:Gliosarcoma / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D007165:Immunosuppression Therapy / Q000379:methods*; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000494:pharmacology; D009368:Neoplasm Transplantation; D015213:Neuroimmunomodulation / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors
D019496:Cancer Vaccines; D007371:Interferon-gamma