Nature Medicine interpretation! How does melanoma trick the host body's immune system into increasing its tolerance to chemotherapy?

October 27, 2020 // -- Complex human immune systems have evolved into an effective protective system against a variety of diseases, such as cancer, and the immune system can use a monitoring process called "immune surveillance" to identify and destroy cancer cells; The immune system sometimes presents another personality that promotes tumor formation without destroying cancer cells, a dual behavior that makes it difficult to diagnose prognostic signs and drug development, and in fact, one of the challenges researchers face in oncology research is how to develop better and more effective immunotherapy.
recently, a study published in the international journal Nature Medicine entitled "Midkine rewires the melanoma microenvironment towards a tolerogenic and immune-resistant state", from the Spanish National Cancer Scientists at research at research centers and others have revealed how melanoma cells do not allow host immune systems to detect and detect them so that the host immune system does not attack melanoma cells and turn them into allies; the findings are of great clinical significance and are expected to be applied to other types of cancer research.
Photo Source: CC0 Public Domain In 2017, researchers analyzed the expression of midkine protein in a new animal model after finding that a protein called MIDKINE plays such a key role in melanoma metastasis that its activation determines the potential for tumor metastasis; It was found that high levels of MIDKINE expression were directly related to the high metastasis potential they had, and that blocking MIDKINE's function could inhibit the spread of cancer cells. In this study, researchers made new discoveries that they found a new role of MIDKINE protein in the host immune system that does not attack melanoma cells, but promotes inflammation and melanoma growth.
then analyzed a database from six independent studies and found that a set of genes was directly related to the expression of MIDKINE protein in patients who did not respond to immunotherapy or developed resistance.
researchers tested these observations in animal models, and researcher Soengas said that when we blocked the expression of the MIDKINE protein, two important immune cells, macrophages and T lymphocytes, began to function properly and began to attack tumors. This means that in the treatment of melanoma patients, we should use a dual treatment, the brake pedal of the immune response, that is, the use of immuno-checkpoint inhibitors is obviously not enough, MIDKINE protein should also be suppressed, so that the body's immune defense system can return to normal function.
also studied other types of tumors, such as gliomas, lung cancer and kidney cancer, which they believe could have a considerable impact on future treatments for many diseases.
In recent years, researchers and clinicians have made considerable efforts to increase the body's immune cells' ability to fight cancer, but even if in some cases immunotherapy has been very successful, this approach needs to be further developed, for example, immunotherapy does not appear to be very successful in treating pancreatic cancer, and in the treatment of melanoma, about 60 percent of patients respond to the treatment.
Differences in tumor response to immunotherapy can lead to tumors being classified as "hot" or "cold" and some "hot" do not fully respond to the treatment, a fact that researchers have previously failed to explain, and the results of this paper are expected to help researchers explain why this happens, which may help increase the effectiveness of immunotherapy in treating these tumors.
() References: Cerezo-Wallis, D., Contreras-Alcalde, M., Troulé, K. et al. Midkine rewires the melanoma microenvironment towards a tolerogenic and immune-resistant state. Nat Med (2020). doi:10.1038/s41591-020-1073-3 How melanomaes the immune system, the resistance to the immunotherapyby The Spanish National Cancer Research Center