Death to traitors!
A way to kill cancer-protecting T-cells has been found
Sergey Kolenov, Hi-tech+
In oncological diseases, some immune cells stand up to protect the tumor. It is not easy to cope with them without harming the whole body. However, an international group of researchers managed to find a vulnerable spot in the "traitor" lymphocytes.
Regulatory T cells play an important role in healthy tissues, preventing autoimmune reactions and promoting wound healing. Unfortunately, in some oncological diseases, they turn to the "dark side" and begin to protect the tumor from attacks by the immune system and immunotherapy. Unfortunately, simply suppressing the activity of regulatory T-lymphocytes can lead to serious autoimmune diseases. This means that a different approach is needed to neutralize them.
Specialists from the Ludwig Institute for Cancer Research presented their view on this problem, whose work is described in the press release Targeting turncoat immune cells to treat cancer. They noticed that an environment with high acidity is formed in the center of the tumor, where there is not enough oxygen and nutrients. This causes the regulatory T-lymphocytes present here to change their metabolism.
According to the researchers, the need to adapt to a specific environment can form new vulnerabilities in regulatory T cells. To detect them, the team compared the expression of T-lymphocyte genes isolated from blood and from breast tumors.
It turned out that the expression of several genes associated with lipid metabolism was increased in tumor regulatory T cells. First of all, we are talking about the CD36 receptor gene, which is involved in the absorption of lipids. The analysis of lymphocytes obtained from patients with melanoma gave similar results.
To clarify the role of CD36, scientists conducted an experiment with mice in whose T-lymphocytes the gene for this receptor was absent. During the experiment, it turned out that such individuals are much less vulnerable to melanoma. At the same time, the number and functions of regulatory T cells were lower than usual only inside tumors, but not in healthy tissues.
When CD36 antibodies were used to treat normal mice suffering from melanoma, the animals experienced a reduction in the number of intracellular T cells. And the combination of antibodies with one of the types of immunotherapy – blockade of the PD-1 pathway - slowed down the growth of the tumor, which significantly prolonged the life of the mice. No side effects were found in this case.
Currently, researchers are developing anti-cancer therapy based on the results obtained. In addition, they analyze how a decrease in the number of regulatory T-lymphocytes may affect other types of tumors.
Article Wang et al. CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors published in the journal Nature Immunology – VM.
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