Scientists talked about the role of immune cells in the spread of cancer
The spread of cancer to other organs is one of the most dangerous stages in the development of cancer. At the same time, the ability of tumor cells to move around the body is influenced not only by their own properties, but also by the cells that are next to them. Scientists have discovered that some elements of the immune system can create conditions for cancer cells to enter a state associated with the formation of metastases. The information about which cells are involved in this process and how they interact with the tumor can be found in the Izvestia article.
Different cells around the tumor
Researchers from the Free University of Brussels have studied how immune cells interact with tumors at different stages of the epithelial-mesenchymal transition (EMT). The results of the work are published in the journal Nature Cancer.
EMT is a process during which cancer cells gradually lose their strong connections with neighboring cells and acquire the ability to move more actively. During this transition, they go through an intermediate, or hybrid, stage. According to the researchers, it is cells in this state that have a particularly high ability to form metastases.
Scientists have noticed that the tumor does not consist only of cancer cells. It also contains ordinary body cells, including elements of the immune system and blood vessels. The researchers decided to find out which immune cells are located next to the tumor cells at different stages of EMT and how the interaction between them affects the spread of the disease.
It turned out that different stages of cellular transition have their own microenvironment. Hybrid tumor cells were more often found next to neutrophils, a type of white blood cell. At a later stage of EMT, macrophages, which also belong to cells of the immune system, were predominantly found next to cancer cells.
Neutrophils and macrophages
To test the role of these cells, the researchers conducted experiments on mice and individually removed neutrophils and macrophages from the body. The results were different. After neutrophil removal, the number of hybrid tumor cells decreased. At the same time, the animals had significantly fewer lung metastases. When the scientists removed macrophages, the number of hybrid cells, on the contrary, increased. However, the number of lung metastases did not change.
Anki Dong, one of the first authors of the study
It was amazing to see that neutrophils and macrophages occupy different territories around cancer cells. When we removed the neutrophils from the mice, the number of hybrid cancer cells decreased significantly, and more importantly, this led to a dramatic decrease in the number of metastases.
Thus, in experiments, neutrophils were associated with the formation of a hybrid state of tumor cells and the spread of cancer to the lungs. Macrophages also affected EMT, but their removal did not lead to a reduction in metastases. The authors emphasized that these results show different functions of the two types of immune cells, rather than the same effect of the entire immune system on the tumor.
Two signals for cancer cells
The scientists then found out which molecules help neutrophils and macrophages interact with tumor cells. It turned out that neutrophils secrete oncostatin M, a molecule that promotes the transition of cancer cells to the hybrid state of EMT. When mice were injected with a drug that blocks oncostatin M, the number of such cells decreased.
Macrophages, in turn, secrete another signaling protein, TGFß1. It triggers the epithelial-mesenchymal transition and promotes the advancement of tumor cells to its most advanced stage.
Sebastian Vanuytven, co-author of the study
By analyzing for the first time the molecular interaction between immune and tumor cells during EMT, we identified oncostatin M and TGFß1 as two key molecules regulating this process and the spread of metastases.
Thus, the researchers described two different signaling mechanisms. Oncostatin M is associated with the appearance of hybrid tumor cells, and TGFß1 is associated with the transition to a later stage of EMT. At the same time, the experiment with blocking oncostatin M showed a reduction in the number of hybrid cells in mice, but by itself it does not prove that such an approach can prevent metastases in humans.
What was found in human tumors
To test whether the described mechanisms can occur in human cancers, the researchers studied samples of human tumors. They found oncostatin M-producing neutrophils next to hybrid cancer cells in breast, pancreatic, lung, and bladder tumor samples.
According to the authors, this indicates that a similar interaction of immune and tumor cells can occur in some types of cancer in humans. However, the detection of neutrophils and oncostatin M in tissue samples does not yet prove that blocking this molecule will help patients or reduce the likelihood of metastasis.
Cedric Blanpin, Head of the study
EMT in cancer cells and the ability to metastasize are determined not only by the cancer cells themselves, but also depend on the molecular interaction between white blood cells and cancer cells. It is important to assess whether exposure to the identified signaling molecules, in particular oncostatin M, will prevent the formation of metastases and increase the sensitivity of tumors to anti-cancer therapy.
So far, the work reveals one of the mechanisms of the tumor's interaction with the immune system, but it does not offer a ready-made treatment method. The main experiments with removing immune cells and blocking oncostatin M were conducted in mice, and the results of analysis of human tumors confirm the presence of a similar mechanism only in some samples.
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