Barrier for metastases
Scientists have proposed a new way to fight metastases
Swiss biologists have studied the mechanism of transition of cancer cells remaining after tumor treatment from a dormant state to an active one, which leads to the formation of metastases, and also proposed options for blocking the "awakening" of cancer cells. The results of the study are published in the journal Nature (Correia et al., Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy).
Even after removal, a cancerous tumor can leave a sinister legacy in the body. Years after apparently successful treatment, metastases may begin to develop in the body. They originate from cancer cells that migrate from the original tumor to other organs and can be there in a "hibernation", or dormant state for a considerable time. One of the biggest questions in cancer research is what exactly is causing this transition.
"The dormant period provides an important therapeutic window during which the number of cancer cells and their heterogeneity are still manageable," the press release says. The words of Professor Mohamed Bentires-Alj of the University of Basel, the head of a joint study conducted by the staff of the Department of Biomedicine of the University and the doctors of the University Hospital Basel. "Therefore, understanding the cellular and molecular mechanisms underlying tumor dormancy is crucial to prevent cancer recurrence."
Using mouse models and human tissue samples, the authors traced how cancer cells that initially migrated from the breast tumor to the liver remained inactive or awakened with the formation of metastases.
It turned out that two types of cells play a key role in this transition. On the one hand, these are natural killer cells - cells of the immune system that usually kill abnormal or infected cells, as well as slow down their proliferation. Killer cells secrete the cytokine gamma interferon, which keeps cancer cells dormant. On the other – stellate liver cells. When they are activated, they suppress immune cells, which allows cancer cells to awaken from hibernation.
"There may be different reasons why stellate liver cells are activated: for example, chronic inflammation in the body or persistent infection," explains the first author of the article, Dr. Anna Correia.
The authors propose several possible methods for preventing metastases: immunotherapy based on interleukin-15, which increases the number of natural killer cells in the tissue; interferon gamma therapy, which supports the dormant state of cancer cells; and inhibitors of the mechanism by which stellate liver cells paralyze natural killer cells. Appropriate treatments already exist for all of these approaches, but they still need clinical trials.
"Our results give hope for immunotherapy that focuses on stimulating natural killer cells as a preventive strategy for patients with dormant cancer cells and the risk of developing metastases," says Bentires-Alge.
"We have proven that these cells are a natural barrier against liver metastases," adds Correia. "If they can be used to prevent the development of metastases in other parts of the body, it can permanently prevent cancer recurrence."
The authors note that they are now faced with the task of demonstrating that the activation of natural killer cells prevents metastasis in humans.
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