Repair proteins protect cancer cells from T cell attack

Cancer cells are extremely adept at resisting the body’s defenses. They are also able to do this because they can repair themselves very quickly during an immune cell attack with the help of special proteins. Alex Ritter’s team from the US biotechnology company Genentech has now presented the protective measure for cancer cells in the journal Science.

Certain immune cells, the cytotoxic T lymphocytes, are specialized in destroying infected cells and tumor cells. Once they have found their target, they release various cell toxins: the protein perforin forms pores in the cell membrane, through which the enzyme granzyme can enter the cell. There it initiates programmed cell death, apoptosis. However, as Ritter’s team discovered, cancer cells have found an effective way to protect themselves from T-cell attacks: they form protein complexes called Endosomal Sorting Complexes Required for Transport (ESCRT), which close the small pores. As a result, granzymes are less able or unable to penetrate the tumor cell and switch it off.

First, the researchers observed the ESCRT proteins inside cancer cells in real time using a special laser microscope. They found that the ESCRT proteins migrated to the damaged cell membrane immediately after a T cell attack. In another experiment, the researchers blocked the function of the protein complexes. The defense cells were then able to kill more tumor cells than before.

Cancer cells have developed a number of additional strategies to evade the immune system: The malignant cells can make themselves “invisible” to the immune system by hiding their typical surface molecules. Some cancer cells are also able to bind to T cells and slow them down. With the help of immunotherapies, doctors want to circumvent these mechanisms so that the cancer cells can no longer escape the body’s own defences.

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