Scientists identify a new and surprising function of a membrane protein on the surface of cancer cells: It supports and stabilizes an important 'co-stimulatory' factor that enhances the activation of T cells, thus improving the immune response against the tumor.
Scientists from the German Cancer Research Center identify a new and surprising function of a membrane protein on the surface of cancer cells: It supports and stabilizes an important"co-stimulatory" factor that enhances the activation of T cells, thus improving the immune response against the tumor. The study was conducted in collaboration with researchers from the Netherlands Cancer Institute.
T cells are the key players in the immune defense against tumors. Their activation is tightly controlled by a variety of inhibitory and also stimulatory immune checkpoints. However, tumor cells often sabotage this system by manipulating the expression of checkpoint proteins to escape destruction by the immune system.
"It is intriguing to observe that many cancer cells inherently express CD58, a molecule that essentially contradicts their own survival when they come under immune attack. We therefore wanted to understand what controls the expression of CD58," says Chong Sun, an immunologist at the German Cancer Research Center.
Moreover, using a model of TCR-T cell treatment in the culture dish, the researchers showed that CMTM6 loss from tumor cells impairs T cell activation. They also found that the influence of CMTM6 on CD58 plays an important role in the antigen-specific interaction of T cells with tumor cells and also affects the response to PD-L1 blockade.
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