Against your own and others '

In order for a malignant tumor to grow and spread, it must avoid the attack of immune cells, especially specialized killer cells - T-killers. A group of researchers from the Salk Institute for Biological Research, led by Professor Susan Kayech, found out that the environment around cancer cells (the tumor microenvironment) contains a large amount of oxidized lipids, which, when in contact with T-killers, suppress the ability of the latter to kill cancer cells. In a vicious circle, T cells, needing energy, increase the level of CD36, a cellular fat carrier, which saturates T cells with even more oxidized fat and further inhibits their antitumor functions. Researchers have found new ways to preserve the immune system's ability to fight cancer by reducing the damaging effects of lipids on T-killers. The identification of such factors that cause suppression of immunity in the tumor microenvironment will help to improve the methods of cancer immunotherapy.

Scientists already know that tumors accumulate fats and that this is due to immune dysfunction, but the details of the relationship were not clear. Collaborating with colleagues from the University of California at San Diego and Yale University, the group found that the tumor contains an increased amount of several classes of lipids, including oxidized lipids, which are usually a component of oxidized low-density lipoproteins (LDL), considered "bad" fats. The researchers observed how T-killers react to oxidized LDL in tumors, and found that in such a microenvironment, T cells increase CD36 expression on their surface and absorb a large amount of oxidized lipids. This process served as a catalyst for even greater oxidation of lipids inside T-killers and eventually suppressed their antitumor activity.

The team investigated how CD36 interferes with T cell function in vivo in mouse models lacking CD36 and in vitro using CD36-blocking antibodies. The researchers confirmed that CD36 contributes to the dysfunction of T cells in tumors by increasing the absorption of oxidized lipids, which causes the activation of the stress response protein p38 and inhibition of antitumor activity.

The researchers also evaluated therapeutic possibilities for reducing lipid oxidation and restoring the function of T-killers in tumors in vitro by blocking CD36 antibodies and in vivo by increased expression of glutathione peroxidase 4 (GPX4), capable of removing oxidized lipids from cells.

It is important to note that lipid oxidation occurs not only in T-lymphocytes, but also in cancer cells, and their excess can lead to cell death. Many researchers are trying to increase lipid oxidation in cancer cells to a lethal level, but Kaech and her group urge some caution. The discovered vulnerability of T cells to lipid oxidation may require the search for more selective approaches to inducing lipid oxidation in tumor cells that does not affect T lymphocytes; otherwise, antitumor T cells can also be destroyed.

Article by S.Xu et al. An uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors is published in the journal Immunity.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to the Salk Institute for Biological Studies: "Bad fat" suppresses killer T cells from attacking cancer.