Escort service
Immune Escort helps cancer metastasize
Kirill Stasevich, "Science and Life"
We know that the immune system must hunt not only for infection, but also for malignant cells. However, it often turns out that the immune system helps the tumor, albeit unwittingly. In particular, we have written several times about how immune cells help cancer to metastasize: in one case, we were talking about DNA networks produced by neutrophils - these networks help tumor cells penetrate into healthy tissues; in another case, we were talking about monocytes that help cancer cells get out of the tumor and go to colonize new places.
Another mechanism of involuntary immune assistance to cancer is described in a recent article in Nature by employees of the University of Basel and the Swiss Higher Technical School of Zurich (Szczerba et al., Neutrophils escort circulating tumour cells to enable cell cycle progression).
They noticed that circulating cancer cells in the blood often go in the company of white blood cells, among which the majority are neutrophils. And neutrophils obviously helped cancer: breast cancer patients developed the disease faster if their circulating cancer cells floated with such an immune escort.
Drawing from the press release of the University of Basel Escort service: The role of immune cells in the formation of metastases – VM.
In experiments on mice, it was possible to directly show that cancer cells receive some advantage from immune support. When cancer cells taken from one mouse were released from immune cells, and then injected into other mice in such a "naked form", these mice had more metastases than when they were injected with cancer cells that were initially without immune accompaniments. Finally, when the number of neutrophils was simply reduced in mice, they had fewer immune-cancer cell clusters and at the same time fewer metastases.
Later it turned out that cancer cells that used an immune escort have more active genes and molecular signaling pathways that stimulate cell division. That is, having settled in place, such cells colonize healthy tissue faster, they will form a tumor faster here. But cancer cells come to such a state of heightened readiness thanks to immune signaling proteins – cytokines IL-1ß and IL-6, synthesized by neutrophils of accompaniment (cancer cells themselves have more receptors for these proteins). If individual cancer cells were treated with IL-1ß and IL-6 cytokines, they then metastasized more successfully – more secondary tumors appeared in the lungs of the experimental mice to whom they were injected. Accordingly, when cancer cells were deprived of receptors for immune proteins, their activity of immune signals stimulating division decreased.
But such immune-cancer cell clusters are not found in all patients. Obviously, in some cases, cancerous tumors are somehow particularly predisposed to use immune cells and their proteins for their own purposes. Indeed, the authors of the work found that primary tumors, whose cells are sent on a journey with a neutrophil escort, have special mutations – in particular, in the TLE1 gene, although exactly how these mutations help to establish contact with neutrophils is still unclear. It was also found out that one of the membrane proteins responsible for intercellular connections is important for the formation of an immune-cancer cluster. Perhaps similar clustering happens with other types of tumors, not only with breast cancer, but whether it is so or not, you need to check experimentally.
We repeat that this is not the first time that neutrophils are noticed in involuntary indulgence of cancer – in addition to the DNA networks mentioned at the beginning, other mechanisms are triggered here, and the described immune escort only adds another item to the list. For some reason, neutrophils, whose main task is to be the first to meet an infection, turned out to be a particularly weak link in the case of cancer.
But this only means that in this case you need to pay special attention to them. Perhaps some means that will allow you to influence the behavior of neutrophils (or simply selectively reduce their number) will help at least in some individual cases to reduce the likelihood of metastases.
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