Definitive evidence that natural killer (NK) cells inhibit experimental tumor metastases in vivo
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Abstract:
Effector lymphoid cells that inhibit hematogenous tumor metastasis in normal unimmunized mice were studied. Mice pretreated with cyclophosphamide (Cy) exhibited a diminished ability to destroy circulating tumor cells, which, in turn, caused an increased incidence of experimental pulmonary metastasis. Adoptive transfer of spleen cells from unimmunized syngeneic donors abrogated the Cy-induced enhancement of metastasis formation. The effector cell active in these adoptive transfer experiments was sensitive to treatment with specific anti-NK-1.2 antibodies and complement. This treatment was shown by in vitro tests to deplete or inactivate NK cells selectively. These findings provide direct evidence that NK cells play a significant role in the inhibition of hematogenous tumor metastases in vivo.
Insights
Natural killer (NK) cells prevent tumor spread in mice. Depleting NK cells increased metastasis, while transferring NK cells reduced it, confirming their crucial role in inhibiting cancer metastasis.
Area of Science:
- Immunology
- Cancer Biology
- Oncology
Background:
- Hematogenous tumor metastasis is a major cause of cancer mortality.
- The role of innate immune cells in preventing metastasis in vivo is not fully understood.
Purpose of the Study:
- To investigate the role of effector lymphoid cells in inhibiting hematogenous tumor metastasis.
- To identify the specific immune cell type responsible for preventing tumor spread in normal mice.
Main Methods:
- Mice were treated with cyclophosphamide (Cy) to assess its effect on metastasis.
- Adoptive transfer of spleen cells was performed to evaluate the protective capacity of immune cells.
- Specific anti-NK-1.2 antibodies and complement were used to deplete natural killer (NK) cells.
Main Results:
- Cyclophosphamide treatment led to increased experimental pulmonary metastasis, indicating impaired destruction of circulating tumor cells.
- Adoptive transfer of spleen cells abrogated the Cy-induced enhancement of metastasis.
- The effector cell responsible for inhibiting metastasis was identified as NK cells, sensitive to anti-NK-1.2 antibody treatment.
Conclusions:
- Natural killer (NK) cells play a significant role in inhibiting hematogenous tumor metastasis in vivo.
- NK cells are crucial for preventing the formation of experimental pulmonary metastases in normal mice.