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Effect of systemic administration of mouse recombinant interferon-gamma on the lung tumor metastases in mice
1Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Abstract:
The purpose of this study was to examine the effective anti-metastatic activity by multiple i.v. administrations of mouse recombinant interferon-gamma (IFN-gamma) against pulmonary metastases of 3LL or B16-BL6 melanoma cells after surgical excision of primary tumors. Multiple treatments with IFN-gamma reduced effectively the incidence of pulmonary tumor metastases. Repeated 4 consecutive treatment modalities with IFN-gamma showed remarkable reduction of lung tumor colonies, and also rendered alveolar macrophages (AM) cytotoxic against B16-BL6 cells. In contrast, 14 consecutive administrations of IFN-gamma at any doses (10(2) and 10(3) U/mouse) could not activate macrophages to become cytotoxic, but were effective in regressing metastases. Thus, antimetastatic activity of IFN-gamma may be due to the stimulation of host immune defense systems such as induction of tumoricidal macrophages, presumably the direct antiproliferative action to tumor cells, or both actions under the appropriate administration conditions. We found that the systemic administration of IFN-gamma under appropriate multiple treatment modalities results in the reduction of the lung metastases and can activate AM to become tumor cytotoxic at relatively low doses (10(2) U). High-dose IFN-gamma in the multiple administration schedule was also effective for the reduction of lung tumor colonies, but strongly suppressed the nonspecific immune function and could not activate tumoricidal properties of AM.
Insights
Multiple administrations of mouse recombinant interferon-gamma (IFN-gamma) effectively reduced lung metastases. This immunotherapy activated immune cells to fight cancer, demonstrating its anti-metastatic potential.
Area of Science:
- Immunology
- Cancer Research
- Pharmacology
Background:
- Metastasis is a major challenge in cancer treatment.
- Interferon-gamma (IFN-gamma) is a cytokine with known immunomodulatory effects.
- Understanding IFN-gamma's anti-metastatic mechanisms is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the anti-metastatic activity of mouse recombinant interferon-gamma (IFN-gamma) against pulmonary metastases.
- To determine the effects of multiple intravenous administrations of IFN-gamma on melanoma cell metastasis.
- To explore the role of IFN-gamma in activating immune cells, specifically alveolar macrophages (AM), for anti-tumor activity.
Main Methods:
- Surgical excision of primary tumors in mice.
- Multiple intravenous administrations of mouse recombinant IFN-gamma.
- Assessment of pulmonary metastases incidence and lung tumor colonies.
- Evaluation of alveolar macrophage (AM) cytotoxicity against B16-BL6 melanoma cells.
Main Results:
- Multiple IFN-gamma treatments significantly reduced the incidence of pulmonary metastases.
- Repeated IFN-gamma administration (4 consecutive treatments) reduced lung tumor colonies and induced AM cytotoxicity.
- Extended IFN-gamma administration (14 consecutive treatments) did not activate AM cytotoxicity but still regressed metastases.
- Low-dose IFN-gamma (10(2) U) activated AM cytotoxicity and reduced lung metastases.
- High-dose IFN-gamma suppressed non-specific immune function while reducing lung tumor colonies.
Conclusions:
- Systemic administration of IFN-gamma under appropriate multiple treatment modalities effectively reduces lung metastases.
- IFN-gamma can activate alveolar macrophages (AM) to become tumor-cytotoxic, particularly at lower doses.
- The anti-metastatic activity of IFN-gamma may involve stimulating host immune defenses, direct anti-proliferative effects on tumor cells, or both.
- High-dose IFN-gamma, while effective in reducing tumor burden, can suppress immune function.