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Local and systemic response of mice to interferon-alpha 1-transfected Friend leukemia cells
L Gabriele1, T Kaido, D Woodrow
1Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Abstract:
DBA/2 mice were injected subcutaneously with an interferon (IFN)-alpha/beta-resistant line of Friend erythroleukemia cells (FLC) transfected with the mouse IFN-alpha 1 gene. These tumor cells produced IFN constitutively, and mice had persistently high levels of IFN in the circulation. We examined the IFN-induced host mechanisms responsible for the local inhibition of growth of these IFN-alpha-transfected FLC and some of the unusual systemic effects of constant interferonemia such as extramedullary hematopoiesis in the liver, an increase in myeloid cells in the spleen, and persistently elevated splenic natural killer (NK) cell activity. In addition, both DBA/2 +/bg and beige mice developed a rapid and specific resistance to intravenous challenge with parental FLC. In previous experiments DBA/2 beige mice could not be protected by exogenous IFN-alpha/beta. The differences in the response of mice to the constitutive production of IFN-alpha by IFN-alpha-transfected tumor cells and their response to exogenous IFN is discussed in terms of the effects of IFN on the host and of antitumor therapy.
Insights
Mice with tumors producing interferon (IFN) showed inhibited tumor growth and enhanced natural killer (NK) cell activity. This study reveals how constant interferonemia impacts host immunity and resistance to cancer.
Area of Science:
- Immunology
- Cancer Biology
- Virology
Background:
- Friend erythroleukemia cells (FLC) are often resistant to interferon (IFN).
- Constitutive IFN production by tumor cells can alter the host immune response.
- Understanding IFN-induced mechanisms is crucial for cancer therapy.
Purpose of the Study:
- To investigate host mechanisms inhibiting the growth of IFN-alpha-transfected FLC.
- To explore systemic effects of sustained interferonemia in mice.
- To analyze differences in host response to endogenous versus exogenous IFN.
Main Methods:
- DBA/2 mice were subcutaneously injected with mouse IFN-alpha 1 gene-transfected FLC.
- Monitoring of IFN levels, tumor growth, and host immune cell populations (NK cells, myeloid cells).
- Assessment of resistance to subsequent intravenous FLC challenge in different mouse strains (DBA/2 +/bg and beige mice).
Main Results:
- IFN-alpha-transfected FLC exhibited local growth inhibition in mice.
- Systemic effects included extramedullary hematopoiesis in the liver and increased splenic myeloid cells.
- Mice developed resistance to parental FLC challenge, particularly notable in beige mice.
- Splenic natural killer (NK) cell activity was persistently elevated.
Conclusions:
- Constitutive IFN production by tumor cells can induce potent anti-tumor immunity and resistance.
- Host responses to endogenous IFN differ from those to exogenous IFN, impacting therapeutic strategies.
- Sustained interferonemia triggers significant immunological and hematological alterations.
