Sneaky Cells

To confuse enemy anti-aircraft missiles and guns, bombers would unload chaff, metallic materials, to confuse the target location. Now we see that malignant cells can do the same with exosomes having protein markers to confuse the immune system.

As Chen et al note in Nature:

Here we report that metastatic melanomas release extracellular vesicles, mostly in the form of exosomes, that carry PD-L1 on their surface. Stimulation with interferon-γ (IFN-γ) increases the amount of PD-L1 on these vesicles, which suppresses the function of CD8 T cells and facilitates tumour growth. In patients with metastatic melanoma, the level of circulating exosomal PD-L1 positively correlates with that of IFN-γ, and varies during the course of anti-PD-1 therapy. The magnitudes of the increase in circulating exosomal PD-L1 during early stages of treatment, as an indicator of the adaptive response of the tumour cells to T cell reinvigoration, stratifies clinical responders from non-responders. Our study unveils a mechanism by which tumour cells systemically suppress the immune system, and provides a rationale for the application of exosomal PD-L1 as a predictor for anti-PD-1 therapy.

NCI also notes:

A new study has identified what may be an important and previously unknown route by which tumors evade the immune system: They secrete small membrane-encased sacs, called exosomes, that are studded with a protein that dials down the immune response. The study, led by researchers at the University of Pennsylvania, found that in lab models of the skin cancer melanoma and in humans with the disease, tumor cells release exosomes coated with proteins called PD-L1. These proteins are part of a family of immune checkpoint proteins that bind to partner molecules on immune cells, effectively deactivating them. The researchers likened the PD-L1-studded exosomes to a fleet of drones engaged in preemptive strikes, moving throughout the body to thwart an antitumor attack before immune cells—namely those known as cytotoxic T cells—ever have a chance to reach the tumor.

Thus the battle between a malignant cell and the attempts to stop them goes on. Every time one thinks they have solved the problem, new information arises that thwarts the attempt.