Could lung cancer exosomes induce apoptosis of natural killer cells through the p75NTR–proNGF–sortilin axis?

Lung cancer is the leading cause of cancer-related death worldwide. Tumor exosomes play an important role in the development of lung cancer. Previous studies indicated that tumor exosomes derived from lung cancer cells contained abundant sortilin. Sortilin is a member of the vacuolar protein sorting 10 protein (VPS10P) family of receptors that act as co-receptors for p75NTR and play an independent role in cell death induced by proNGF. Recently, a study showed that proNGF could mediate the death of natural killer (NK) cells through binding to the p75NTR-sortilin complex. However, it has not been reported, to our knowledge, that lung cancer cells induce NK cell apoptosis through a p75NTR-proNGF-sortilin mechanism. As a secreted protein, lung cancer cells may release some proNGF into the tumor microenvironment. We therefore hypothesized that lung cancer cells may promote the apoptosis of NK cells through releasing exosomal sortilin and proNGF. To test this hypothesis, experiments involving the production of exosomal sortilin and proNGF in lung cancer cells and the expression of p75NTR in NK cells are required based upon previously established experiments using fluorescent components. Such experiments may provide insight into the potential mechanism by which lung cancer cells promote apoptosis of NK cells through a p75NTR-proNGF-sortilin pathway.